๐Ÿ”ท ื”ืžืกืœื•ืœื™ื ื”ื‘ื™ื•ืœื•ื’ื™ื™ื ืฉืžืฉืงืžื™ื ืืช ื”ื’ื•ืฃ: p53 โ€” ืฉื•ืžืจ ื”ื’ื ื•ื – ื—ืœืง ื“โ€™ โ€” ื™ืจื•ืŸ ืžืจื’ื•ืœื™ืŸ

ื—ืœืง ื’' – ืขืœ ื”ื”ื—ืœืžื”

ื—ืœืง ื”' – ืขืœ ื—ืœื‘ื•ื ื™ ื”ื”ื—ืœืžื”

ื›ืฉื ืฉืืœ ืคืขื ื”ืจืงื“ืŸ ื”ื™ืจื•ืฉืœืžื™ (ื‘ืื—ืช ื”ืกื“ื ืื•ืช ืฉื”ืขื‘ื™ืจ ืœืชืœืžื™ื“ื™ื•) ืฉืืœื” ืžื•ืจื›ื‘ืช ืขืœ ื—ื™ื™ ืื“ื, ื”ื•ื ืœื ืžื™ื”ืจ ืœืคืชื•ื— ืืช ืกืคืจื™ ื”ืœื™ืžื•ื“, ื’ื ืœื ืืช ื›ืชื‘ื™ ื”ื—ื›ืžื™ื.

ื‘ืžืงื•ื ื–ืืช ื”ืœืš ื‘ืจื’ืœ ืœื‘ื™ืชื•, ืฆืขื“ ืœืื•ืจืš ื”ื—ื•ืžื•ืช ืฉืœ ื”ืขื™ืจ ื”ืขืชื™ืงื”, ื”ืชื‘ื•ื ืŸ ื‘ืžื“ื‘ืจ ื™ื”ื•ื“ื”, ื•ื‘ื“ืง ืืช ืขืฆืžื•: "ื”ืื ื”ืฉืืœื” ื”ื–ื• ื ื•ื’ืขืช ื’ื ืืœื™ื™? ื”ืื ื’ื ืื ื™ ืฆืจื™ืš ืœืชืงืŸ ื›ืืŸ ืžืฉื”ื•?"

ืจืง ืื—ืจื™ ืฉื‘ื“ืง ืืช ืขืฆืžื• ื•ืชื™ืงืŸ ืืช ืžื” ืฉื ื“ืจืฉ ืœืชืงืŸ โ€” ื—ื–ืจ ื•ืขื ื”.


๐Ÿ”ท ื”ื”ึดืฉึฐืืชึธึผื”ื•ึผืช

ื™ืฉ ืจื’ืข ืฉื‘ื• ื”ื—ื™ื™ื ืื™ื ื ืžืชืงื“ืžื™ื โ€” ื”ื ืžืฉืชื”ื™ื. ืขื‘ื•ืจ ื”ืคื™ืœื•ืกื•ืคื™ื ื”ื™ื•ื•ื ื™ื, "ืคื ืื™"

ืกืงื•ืœื” (Schole) – ื”"ืคื ืื™" (ื‘ื™ื•ื•ื ื™ืช: Schole, ื”ืžืงื•ืจ ืœืžื™ืœื” School) ืœื ื”ื™ื” ืžื ื•ื—ื” ืคืกื™ื‘ื™ืช, ืืœื ื–ืžืŸ ืฉืžื•ืงื“ืฉ ืœืœืžื™ื“ื”, ื”ืชื‘ื•ื ื ื•ืช ื•ืฆืžื™ื—ื” ืจื•ื—ื ื™ืช ืœืœื ืœื—ืฅ ืฉืœ ืขื‘ื•ื“ื” ืื• ืฆืจื›ื™ื ื”ื™ืฉืจื“ื•ืชื™ื™ื. ื”ื”ึดืฉึฐืืชึธึผื”ื•ึผืช ื”ืชืงื‘ืœื” ื›ืžืฆื‘ ื”ืื™ื“ื™ืืœื™ ืฉืžืขื ื™ืง ืœืื“ื ื”ื–ื“ืžื ื•ืช ืœื”ืชื‘ื•ื ื ื•ืช ืžืขืžื™ืงื” (Contemplation) ื‘ืขื•ืœื, (Contemplation) ื•ื—ื™ืคื•ืฉ ืื—ืจ ืืžืช, ื™ื•ืคื™ ื•ื˜ื•ื‘, ืœืœื ืจื“ื™ืคื” ืื—ืจ ืชื•ืฆืื•ืช ืžื™ื™ื“ื™ื•ืช.

ืœื "ืขื™ื›ื•ื‘" (Delay) ืžืขื™ืง ืฉืžืคืจื™ืข ืœื–ืจื™ืžื”, ื•ื‘ื˜ื— ืฉืœื "ื—ืจื“ื”" (Anxiety) ืฉืœ ื—ื•ืกืจ ื•ื“ืื•ืช.
ืœื ื”ื™ื“ืจื“ืจื•ืช โ€”
ื’ื ืœื ืขืฆื™ืจื” ืื• ื“ืžื™ืžื”. ืœืคื™ ื’'ื•ืŸ ื“ื™ื•ืื™, ืžื—ืœื•ืฆื™ ื”ืคื™ืœื•ืกื•ืคื™ื” ืฉืœ ื”ื—ื™ื ื•ืš, ื”ื™ื ืจืคืœืงืฆื™ื”: "ืฉืงื™ืœื” ืคืขื™ืœื”, ืขืงื‘ื™ืช ื•ื–ื”ื™ืจื” ืฉืœ ื”ื™ื“ื•ืข. ืขืฆื™ืจื” ืžื›ื•ื•ื ืช ื›ื“ื™ ืœื‘ื“ื•ืง ืืช ื”ื™ืกื•ื“ื•ืช ืขืœื™ื”ื ื”ืžืฆื‘ ืืœื™ื• ื”ื’ืขื ื• ื ืฉืขืŸ.

ื‘ืชืจื‘ื•ื™ื•ืช ืจื‘ื•ืช ืชื™ืืจื• ืืช ื”ืจื’ืข ื”ื–ื” ื“ืจืš ื“ื™ืžื•ื™ ื—ื–ืง ืื—ื“:
ืขื•ืฃ ื”ื—ื•ืœ ื›ื–ื”ื• ื’ื ื—ืœื‘ื•ืŸ ื”ืคื•ืขืœ ื‘ื’ื•ืคื ื• ื‘ืฉื p53, ื ื•ืฉื ื—ืœืง ื“' ืฉืœ ืจืฆืฃ ื”ืžืืžืจื™ื ืขืœ ื›ื•ื—ื•ืช ื”ื”ื—ืœืžื” ื•ืฆื™ืจื™ ื”ื”ื—ืœืžื” ื”ื‘ื™ื•ืœื•ื’ื™ื™ื ืฉืคื•ืขืœื™ื ื‘ื’ื•ืคื ื• [ืžืงื•ืจ].

ื—ืœื‘ื•ืŸ p53 ืžื›ื•ื ื” "ืฉื•ืžืจ ื”ื’ื ื•ื" (Guardian of the Genome), ื•ื”ื“ืžื™ื•ืŸ ื‘ื™ื ื• ืœื‘ื™ืŸ ืžื•ืฉื’ ื”ืกืงื•ืœื” ื•ื”ื”ึดืฉึฐืืชึธึผื”ื•ึผืช ื ื™ื›ืจ ื‘ืฉืœื•ืฉื” ื”ื™ื‘ื˜ื™ื ืžืจื›ื–ื™ื™ื: [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3, ืžืงื•ืจ4].

1. ื”ื”ืฉืชื”ื•ืช ื›"ื ืงื•ื“ืช ื‘ื™ืงื•ืจืช" (Checkpoint)

ื›ืžื• ืฉื”ืกืงื•ืœื” ืžืฉื”ื” ืืช ื”ืœื—ืฅ ืœื”ื™ื•ืช ื™ืฆืจื ื™ ื›ื“ื™ ืœืืคืฉืจ ืœืžื™ื“ื”, p53 ืžืฉื”ื” ืืช ืžื—ื–ื•ืจ ื”ืชื. [ืžืงื•ืจ1]

  • ื”ืคืขื•ืœื”: ื›ืฉืžื–ื•ื”ื” ื ื–ืง ื‘-DNA, ื—ืœื‘ื•ืŸ p53 ืขื•ืฆืจ ืืช ื—ืœื•ืงืช ื”ืชื ื‘ื ืงื•ื“ืช ื‘ื™ืงื•ืจืช (G1/S).
  • "ื”ื”ึดืฉึฐืืชึธึผื”ื•ึผืช" ื”ื‘ื™ื•ืœื•ื’ื™ืช ืฉื ื•ืฆืจืช ืื™ื ื” ืขื™ื›ื•ื‘ ืžืขื™ืง, ื“ืžื™ืžื”, ืื• ืชื’ื•ื‘ืช ื—ืจื“ื”, ืืœื ื”ึดืฉึฐืืชึธึผื”ื•ึผืช, ื”ืชื‘ื•ื ื ื•ืช ื—ื™ื•ื ื™ืช. ื”ืชื ืฉื•ืงืœ ืžื” ืขืœื™ื• ืœืขืฉื•ืช, ื›ื“ื™ ืœื”ืชื’ื‘ืจ ืขืœ ืžืืžืฆื™ ื”ืื“ื ืœื”ืจื•ืก ืืช ืžืขืจื›ืช ืฆื™ืจื™ ื”ื”ื—ืœืžื” ื‘ืขื–ืจืช ืชื–ื•ื ื” ื”ืจืคืชืงืื ื™ืช, ืื•ืคื ืชื™ืช ื•ื˜ืขื™ืžื” ื›ื“ื‘ืจื™ื•, ืื™ืš ืœื”ืขื‘ื™ืจ ื˜ืขื•ื™ื•ืช ื‘ื™ื•ืœื•ื’ื™ื•ืช ืฉื ื•ืฆืจื•ืช ื•ืžืงื“ืžื•ืช ืžื—ืœื” ื”ืœืื”. [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3]

2. ื‘ื™ืจื•ืจ ื”ื™ื›ืŸ ื˜ืขื™ื ื• ื›ื“ื™ ืœืฉืคืจ (Repair)

ืžื ื’ื ื•ื ื™ ื”ืชื™ืงื•ืŸ [ืžืงื•ืจ1, ืžืงื•ืจ2].

  • ื”ืคืขื•ืœื”: ื‘ืžื”ืœืš ื”ืขืฆื™ืจื”, p53 ืžื’ื™ื™ืก ื—ืœื‘ื•ื ื™ื ืฉืžืชืงื ื™ื ืืช ื”-DNA ื”ืคื’ื•ื.
  • ื”ื”ืงื‘ืœื”: ื–ื•ื”ื™ ื”ืจืคืœืงืฆื™ื” ื”ืœื›ื” ืœืžืขืฉื”. p53 ืœื ืจืง ืื•ืžืจ "ื™ืฉ ื˜ืขื•ืช", ื”ื•ื ืžืืคืฉืจ ืืช ื”ืžืจื—ื‘ (ื”ื–ืžืŸ) ื•ื”ื›ืœื™ื ืœื‘ื—ื•ืŸ ืืช ื”ืžืฆื‘ ืžื—ื“ืฉ ื•ืœืชืงืŸ ืื•ืชื• ืœืคื ื™ ืฉืžืžืฉื™ื›ื™ื ื‘ื—ื™ื™ื (ื‘ื—ืœื•ืงืช ื”ืชื). [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3].

3. ื”ื‘ื ืช ื”"ื ื›ื•ืŸ" ื•ื”ื›ืจืขื” (Cell Fate)

p53 ื”ื•ื ื”"ืคื™ืœื•ืกื•ืฃ" ืฉืœ ื”ืชื โ€“ ื”ื•ื ื”ืฉื•ืžืจ ื”ืืคืœื˜ื•ื ื™ ื•ืžื™ ืฉืฆืจื™ืš ืœื”ื›ืจื™ืข ืžื”ื• ื”ื ืชื™ื‘ ื”ื ื›ื•ืŸ. [ืžืงื•ืจ1, ืžืงื•ืจ2].

  • ื”ืคืขื•ืœื”: ืื ื”ื ื–ืง ื ื™ืชืŸ ืœืชื™ืงื•ืŸ, p53 ืžืืคืฉืจ ืœืชื ืœื”ืžืฉื™ืš ื•ืœื’ื•ืฃ ืœืชืงืŸ. ืื ื”ื ื–ืง ื—ืžื•ืจ ืžื“ื™ ื•ื”ืชื™ืงื•ืŸ ื™ื•ืœื™ื“ ืฉื™ื‘ื•ืฉ (ืกืจื˜ืŸ), ื”ื•ื ืžื•ื‘ื™ืœ ืืช ื”ืชื ืœืืคื•ืคื˜ื•ื–ื™ืก (ืžื•ื•ืช ืชืื™ ืžืชื•ื›ื ืŸ) โ€“ ื”ืงืจื‘ืช ื”ืคืจื˜ ืœืžืขืŸ ืชืงื™ื ื•ืช ื”ืžืขืจื›ืช ื›ื•ืœื”.
  • ื–ื•ื”ื™ ื”ืฉืžื™ืจืช ื”ืžืขืœื”, ื”ื—ืชื™ืจื” ืœืืžืช (ื”ื‘ื ืช ื”ื ื›ื•ืŸ). ื”ื”ืฉื”ื™ื™ื” ื‘ืกืงื•ืœื” ืฉืžื•ืคื™ืขื” ื•ืžื›ื›ื‘ืช ื›ืืŸ. ื”ื™ื ื ื•ืขื“ื” ืœื‘ืจืจ ืžื” ื ื›ื•ืŸ ื•ืžื” ื˜ืขื•ืช. p53 ืžื•ื•ื“ื ืฉืจืง ืžื” ืฉ"ื ื›ื•ืŸ" (DNA ืชืงื™ืŸ) ื™ืžืฉื™ืš ื”ืœืื”. [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3]

ืกื™ื›ื•ื ื”ื”ืฉื•ื•ืื”

ื”ื™ื‘ื˜ ืžืงื•ืจ1,] ืžืงื•ืจ2].ืกืงื•ืœื” / ืจืคืœืงืฆื™ื”ื—ืœื‘ื•ืŸ p53
ื”ืžืฆื‘ื”ืฉืชื”ื•ืช (ื ื™ื ื•ื—ื•ืช, ืขืฆื™ืจืช ื”ืžืจื•ืฅ)Cell Cycle Arrest (ืขืฆื™ืจืช ื—ืœื•ืงืช ื”ืชื)
ื”ืžื˜ืจื”ื‘ื™ืจื•ืจ ื•ืชื™ืงื•ืŸ (ื”ื™ื›ืŸ ื˜ืขื™ื ื•, ืื™ืš ืœืฉืคืจ)DNA Repair (ื–ื™ื”ื•ื™ ืฉื‘ืจื™ื ื•ืชื™ืงื•ื ื)
ื”ืชื•ืฆืื”ืฆืžื™ื—ื” ืžืชื•ืš ืืžืช (ื”ื‘ื ืช ื”ื ื›ื•ืŸ)Genomic Stability (ืฉืžื™ืจื” ืขืœ ื’ื ื•ื ืชืงื™ืŸ)
ืื—ืช ื”ืฉืืœื•ืช ื”ืžืจืชืงื•ืช ืฉืขื•ืœื•ืช ื ื•ื›ื— ื”ืฉื™ื ื•ื™ (ื”ืžื•ื˜ืฆื™ื”) ืฉ"ืฉื•ืžืจ ื”ื’ื ื•ื" (the" โ€œguardian of the genome) p53 ๐Ÿฆโ€๐Ÿ”ฅ ืขื•ื‘ืจ, ื•ืžืฉืชืชืง, ืœื ืžืฉืชื”ื”, ืืœื ืงื•ืจืก, ื ืขื“ืจ ื•ื”ื•ืคืš ืคืกื™ื‘ื™ ื•ืœื ืคืขื™ืœ ื‘ืจื•ื‘ ื”ื’ื™ื“ื•ืœื™ื ื”ืžืžืื™ืจื™ื, ื›ื™ืฆื“ ื”ืฉื•ืžืจ ืฉื”ื˜ื‘ืข ื”ืขื ื™ืง ืœื ื• ื ื”ืจืก ื“ื•ื•ืงื ื›ืฉืื ื—ื ื• ื”ื›ื™ ื ื“ืจืฉื™ื ืœืขื–ืจืชื•โ“[ืžืงื•ืจ].

ื›ืืฉืจ p53 ืคื’ื•ื (ืœืื—ืจ ืฉืขื‘ืจ ืฉื™ื ื•ื™ – ืžื•ื˜ืฆื™ื”), ื”ืชื ืžืื‘ื“ ืืช ื”ื™ื›ื•ืœืช ืœื”ืฉืชื”ื•ืช, ืžืชืขืœื ืžื—ื•ื›ืžืช ื”ื‘ื™ื•ืœื•ื’ื™ื”, ืœื ืžื‘ื—ื™ืŸ ื‘"ื˜ืขื•ื™ื•ืช" ื•ื”ื•ื ืžืชื ื”ืœ ื›ืื™ืœื• P53 ๐Ÿฆโ€๐Ÿ”ฅ ืžืขื•ืœื ืœื ื”ื™ื” ืงื™ื™ื ื•ืžืžืฉื™ืš ืœื”ืฉืชื›ืคืœ ื‘ืคืจืื•ืช โšกโ€“ ื•ื–ื”ื• ื‘ื“ื™ื•ืง ื”ืชื”ืœื™ืš ื”ืกืจื˜ื ื™ [ืžืงื•ืจ]. ื–ื”ื• ื”ื ื•ืฉื ื’ื ืžืฉืœ ืžืจืชืง ืฉืžื•ื’ืฉ ืœืื“ื ื”ื ื”ื ืชืŸ, ืœื—ื‘ืจื” ืื• ืœืื ืฉื™ื ืฉืžืื‘ื“ื™ื ืืช ื”"ืกืงื•ืœื”" ืฉืœื”ื: ื”ื ืžืžืฉื™ื›ื™ื ืœืจื•ืฅ ืงื“ื™ืžื” ื›ืื•ื”ื“ื™ื• ืฉืœ ื‘ื ื™ืžื™ืŸ ื ืชื ื™ื”ื• ืขื ื”ื˜ืขื•ื™ื•ืช ืฉืœื”ื, ืžื‘ืœื™ ืœืขืฆื•ืจ ืœืชืงืŸ, ืขื“ ืœืงืจื™ืกืช ื”ืžืขืจื›ืช ื‘ืชื•ืš ื”ืžืจื—ื‘ ื”ื”ื“ื•ื ื™ืกื˜ื™ ื”ืžื•ืฉื—ืช ืฉื™ืฆืจื• ื•ืงืจืื• ืœื• ื’ืŸ-ืขื“ืŸ ืฉืขื” ืฉื”ื™ื” ืœื’ื™ื”ื ื•ื ืฉืœื”ื [ืžืงื•ืจ1, ืžืงื•ืจ2].

ืื™ืš "ื—ืœื‘ื•ืŸ ื”-p53 ื”ืชื•ื“ืขืชื™" ืฉืœื ื• ื™ื›ื•ืœ ืœืคืขื•ืœ ื˜ื•ื‘ ื™ื•ืชืจ ื‘ื™ื•ืžื™ื•ื?

ืขื•ืฃ ื”ื—ื•ืœ ๐Ÿฆโ€๐Ÿ”ฅ ื”ืžื™ืชื•ืœื•ื’ื™ ืฉื‘ ื•ื ื•ืœื“ ื”ื•ื ืื™ื ื• ื ืœื—ื ื‘ืžืฆื‘ ื”ืงืฉื”.
ื”ื•ื ืžืืคืฉืจ ืœืืฉ ืœืคืขื•ืœ.
ื—ื•ืฉืฃ ืืช ืžืจื›ื™ื‘ื™ื• ื”ื—ื™ื•ื ื™ื™ื ื‘ื™ื•ืชืจ โ€” ื•ืžืชื•ืš ื”ืืคืจ ื”ื•ื ื ื‘ื ื” ืžื—ื“ืฉ.

ืœื ื›ื”ืžืฉืš ื™ืฉื™ืจ ืœื™ืฉ ื”ื™ืฉืŸ โ€”
ืืœื ื›ื”ืชื—ืœื” ืžื“ื•ื™ืงืช ื™ื•ืชืจ. ืจื ืกื ืก, ืฉื™ื‘ืช ืฆื™ื•ืŸ.


ื›ื–ื”ื• ื’ื ืื—ื“ ื”ืžื ื’ื ื•ื ื™ื ื”ืขืžื•ืงื™ื ื‘ื™ื•ืชืจ ื‘ื’ื•ืฃ:

p53 โ€” ืฉื•ืžืจ ื”ื’ื ื•ื.

ื›ืืฉืจ ื”ืชื ืžื–ื”ื” ืขื•ืžืก, ื ื–ืง ืื• ืกื˜ื™ื™ื” ืžื”ืื™ื–ื•ืŸ,
ื”ื•ื ืื™ื ื• ืžืžืฉื™ืš ืœืคืขื•ืœ ื›ืจื’ื™ืœ [ืžืงื•ืจ].

๐Ÿ‘‰ ื”ื•ื ืขื•ืฆืจ.

ืžืืคืฉืจ ืœืžื ื’ื ื•ื ื™ ื”ื‘ื“ื™ืงื” ื•ื”ืชื™ืงื•ืŸ ืœืคืขื•ืœ,
ื•ืจืง ืœืื—ืจ ืžื›ืŸ โ€” ืžืžืฉื™ืš.


ื”ืขืฆื™ืจื” ื”ื–ื• ื”ื™ื ืชื ืื™ ืœื”ื™ืฉืจื“ื•ืชื•. ื‘ื™ื˜ื•ื™ ืœืขื•ืฆืžื”.

ื”ื™ื ื”ื‘ื—ื™ืจื” ืฉืœื ืœื”ืžืฉื™ืš ืœื‘ื ื•ืช
ื›ืืฉืจ ื”ื™ืกื•ื“ื•ืช ืื™ื ื ื™ืฆื™ื‘ื™ื.


๐Ÿ”ถ ืื‘ืœ ื›ืืŸ ืžืชื’ืœื” ื”ืงื•ืฉื™

ื”ื’ื•ืฃ ืื™ื ื• ืคื•ืขืœ ืจืง ื‘ื›ื™ื•ื•ืŸ ืื—ื“.

ื‘ืžืงื‘ื™ืœ ืœืžื ื’ื ื•ืŸ ื”ื‘ืœื™ืžื”,
ืคื•ืขืœ ื‘ื• ื’ื ืžื ื’ื ื•ืŸ ืื—ืจ โ€”
ืžื ื’ื ื•ืŸ ืฉืœ ืฉืคืข, ื‘ื ื™ื™ื” ื•ื’ื“ื™ืœื” [ืžืงื•ืจ].

ืžืกืœื•ืœ ื–ื” ืžื•ื›ืจ ื‘ืฉื:

PI3K โ†’ Akt โ†’ mTOR

[ืžืงื•ืจ].


ื›ืืฉืจ ื”ื•ื ืคื•ืขืœ ื‘ืฆื•ืจื” ืžืื•ื–ื ืช โ€”
ื”ื•ื ื—ื™ื•ื ื™ ืœื—ื™ื™ื.

ื”ื•ื ืžืืคืฉืจ:

  • ื‘ื ื™ื™ื” ืฉืœ ืจืงืžื•ืช
  • ื™ืฆื™ืจืช ื—ืœื‘ื•ื ื™ื
  • ื”ืชื—ื“ืฉื•ืช

๐Ÿ”ด ืืš ื›ืืฉืจ ืื™ืŸ ื”ืคืกืงื”

ื›ืืฉืจ ื”"ืฉืคืข" (ืกื˜ื™ืงื™ื, ืฆ'ื™ืคืก, ืขืœ ื”ืืฉ, ืขื•ื’ื•ืช, ืžืฉืงืื•ืช ืžืžื•ืชืงื™ื… ืืœื›ื•ื”ื•ืœ, ืกื˜ืจืก, ืฉื™ืขื‘ื•ื“ ืœืขื‘ื•ื“ื”) ืžืชืžืฉืš ืœืœื ืขืฆื™ืจื” โ€”

  • ืขื•ื“ืฃ ืžื–ื•ืŸ
  • ืขื•ืžืก ืกื•ื›ืจ
  • ืื•ืชื•ืช ื’ื“ื™ืœื” ืจืฆื™ืคื™ื
  • ื›ื“ื•ืจื™ื ื ื’ื“ ื›ืื‘
  • ื›ื“ื•ืจื™ื ื ื’ื“ ื›ื•ืœืกื˜ืจื•ืœ
  • ื›ื“ื•ืจื™ื ื ื’ื“ ื™ืชืจ ืœื—ืฅ ื“ื
  • ื›ื“ื•ืจื™ื ื ื’ื“ ืกื•ื›ืจืช
  • ื”ืชืžื›ืจื•ืช ืœืขื‘ื•ื“ื”
  • ืกื˜ืจืก
  • ื™ืชืจ ืงื•ืจื˜ื™ื–ื•ืœ

ื”ืžืขืจื›ืช ืžืžืฉื™ื›ื” ืœื‘ื ื•ืช โ€”
ื’ื ื›ืืฉืจ ื”ืชื ืื™ื ืื™ื ื ืžืชืื™ืžื™ื [ืžืงื•ืจ]. ื”ืชื ื‘ื•ื ื”, ื•ื‘ื•ื ื”, ื•ืžื” ื”ื•ื ื‘ื•ื ื”โ“


ื•ื›ืืŸ ื ื›ื ืก ืฉื•ื‘ ืื•ืชื• ืžื ื’ื ื•ืŸ ืฉืงื˜ ืฉืœ ื”ื”ืชื‘ื•ื ื ื•ืช๐Ÿฆโ€๐Ÿ”ฅ, ืขื•ืฃ ื”ื—ื•ืœ ื”ื‘ื™ื•ืœื•ื’ื™ ื” – :

p53 ๐Ÿฆโ€๐Ÿ”ฅ

๐Ÿ‘‰ ืœื ื›ื“ื™ ืœืขืฆื•ืจ ืืช ื”ืชืคืงื•ื“, ืœื ื›ื“ื™ ืœื—ื ืš โ€”
ืืœื ื›ื“ื™ ืœื”ื’ืŸ ืขืœ ื”ืงื™ื™ื [ืžืงื•ืจ].

ื”ื•ื ืžืื•ืชืช:

ืขืฆื•ืจ.
ื‘ื“ื•ืง.
ืชืงืŸ.

ื•ืื™ืŸ ืฉื•ืžืข


๐Ÿ”ป ื”ื‘ืขื™ื” ื”ืืžื™ืชื™ืช

๐Ÿ‘‰ ื”ื‘ืขื™ื” ื”ื™ื ื‘ื›ืš ืฉืื™ืŸ ืœื• ื”ืฉืคืขื” ืขืœ ื”ืืžื•ื ื”, ืขืœ ื”ืœื ืงื™ื™ื, ืขืœ ืขืจื•ืฆื™ ื”ื˜ืœื•ื™ื–ื™ื”, ืขืœ ื”ืกื•ื›ืจ, ืขืœ ื”ืžืœื—… ื•ืœื›ืŸ ื”ื•ื ื ืืœืฅ ืœืขืฆื•ืจ ืฉื•ื‘ ื•ืฉื•ื‘.

ื›ืืฉืจ ื–ื” ืงื•ืจื” โ€”
ื–ื”ื• ืกื™ืžืŸ ืฉื”ืขื•ืžืก, ืฉื”ืื“ื ื”ืžืืžื™ืŸ ื‘ืชื–ื•ื ื” ื”ืื•ืคื ืชื™ืช, ื”ื˜ืขื™ืžื”, ื”ื”ืจืกื ื™ืช ื’ื“ื•ืœ ืžื“ื™, ืื‘ืœ ื”ืื“ื ื‘ืฉืœื•… ื”ืจื•ืคื ืœื ื‘ื“ื™ื•ืง ืงื•ืœื˜ ืžื” ืงื•ืจื” ื‘ืืžืช…


๐Ÿ”ท๐Ÿฅ— ื”ืžื–ื•ืŸ ื›ืชืจื•ืคื”

ื›ื“ื™ ืœื”ื‘ื™ืŸ ืžื” ื™ื•ืฆืจ ืืช ื”ืขื•ืžืก ื”ื–ื”,
ื™ืฉ ืœื”ืขืžื™ืง ื‘ื—ื™ื™ ื”ืื“ื, ืœื ื“ื™ ื‘ื”ืชื‘ื•ื ื ื•ืช ื‘ืžืกืœื•ืœ ื”ืฉืคืข ืขืฆืžื• โ€” ืขืœ-ืžื ืช ืœื”ืืจื™ืš ื—ื™ื™ื, ืœื”ืฆื™ืœ ื—ื™ื™ ืื“ื, ืœื ื“ื™ ื‘ื›ื“ื•ืจื™ื, ื‘ื–ืจื™ืงื•ืช, ื‘ื ื™ืชื•ื—ื™ื, ืฆืจื™ืš ืœื”ื‘ื™ืŸ ืžื” ืžืคืขื™ืœ ืืช ื”ืžื—ืœื” ื•ืžื” ืžืคืขื™ืœ ืืช ื”ืชื—ื–ื•ืงื” ื”ืฉืงื˜ื”, ื•ืžื” ืžืืคืฉืจ, ืžื•ื‘ื™ืœ ื•ืžืงื™ื™ื ืืช ื”ื”ื—ืœืžื” [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3].

ืœื“ืขืช

๐Ÿ‘‰ ื›ื™ืฆื“ ื”ื’ื•ืฃ ืคื•ืขืœ
๐Ÿ‘‰ ื•ืžื“ื•ืข ื”ื•ื ื™ื•ืฆื ืžืื™ื–ื•ืŸ

ืขืœ ื›ืš ื‘ืžืืžืจื™:

ื”p53 ื’ืŸ ืžืงื•ื“ื“ ืœื—ืœื‘ื•ืŸ ืฉืชืคืงื™ื“ื• ื”ืขื™ืงืจื™ ื”ื•ื ืคืงื˜ื•ืจ ืฉืขืชื•ืง, ื›ืœื•ืžืจ ืžืขืœื” ื‘ื™ื˜ื•ื™ื ืฉืœ ื’ื ื™ื ืื—ืจื™ื. ื‘ืžืฆื‘ ื ื•ืจืžืœื™, ืจืžืชื• ื‘ืชืื™ื ื ืžื•ื›ื” ืžืื“, ื•ืจืง ืœืื—ืจ ืฉื ื’ืจื ื ื–ืง ื›ืœืฉื”ื• ืœื“ื "ื ื”ืชืื™ (ืงืจื™ื ื”, ืžื—ืกื•ืจ ื‘ื—ืžืฆืŸ, ืžื—ืกื•ืจ ื‘ื ื•ึผืงึฐืœึตืื•ึนื˜ึดื™ื“ึดื™ื – ืงื‘ื•ืฆื” ืฉืœ ืชืจื›ื•ื‘ื•ืช ืื•ืจื’ื ื™ื•ืช, ื•ื ื–ืงื™ ื™ืชืจ ืฉืœ ืชื–ื•ื ื” ืฉื’ื•ื™ื”: ืฉืžื ื™ื ืžื–ื•ื›ื›ื™ื ื•ืขื•ื“ืฃ ืฉื•ืžืŸ ื˜ืจืื ืก, ื‘ืฉืจ ืื“ื•ื, ื™ืชืจ ื—ืœื‘ื•ืŸ, ืกื•ื›ืจ ื•ืžืœื—, ื—ื•ืžืจื™ ืฆื‘ืข, ืฉื™ืžื•ืจ, ื•ื˜ืขื, ืžื–ื•ืŸ ืžืชื•ืขืฉ, ืกื™ื’ืจื™ื•ืช) ืจืžื•ืช ื”ื‘ื™ื˜ื•ื™ ืฉืœื• ืขื•ืœื•ืช. ื‘ืžืฆื‘ ืชืงื™ืŸ, ื”ื—ืœื‘ื•ืŸ ื ืžืฆื ื‘ืจืžื•ืช ื ืžื•ื›ื•ืช ื•ืžืขื•ื›ื‘ ืขืœ ื™ื“ื™ ื—ืœื‘ื•ืŸ ื‘ืฉื Mdm2, ืฉืžืกืžืŸ ืื•ืชื• ืœืคื™ืจื•ืง, ื•ืžื•ืคืขืœ ืจืง ื‘ืขืช ืฆื•ืจืš [ืžืงื•ืจ1ืžืงื•ืจ2ืžืงื•ืจ3ืžืงื•ืจ4].

Mdm2 (ืื•ื ืงื•ื’ืŸ) ื”ื•ื ื’ืŸ ื•ื—ืœื‘ื•ืŸ ื”ืžื”ื•ื•ื™ื ืจื’ื•ืœื˜ื•ืจ ืฉืœื™ืœื™ (ืžืขื›ื‘) ืžืจื›ื–ื™ ืฉืœ ื”ื—ืœื‘ื•ืŸ P53 ๐Ÿฆโ€๐Ÿ”ฅ, ื”ื™ื“ื•ืข ื›ืžื’ืŸ ืžืฉืžืขื•ืชื™ ืžืคื ื™ ื’ื™ื“ื•ืœื™ื ืกืจื˜ื ื™ื™ื. ืžื ื’ื ื•ืŸ ืคืขื•ืœื”: ื”-MDM2 ื ืฆืžื“ ืœื—ืœื‘ื•ืŸ ื”- (ื”ื ืงืจื "ืฉื•ืžืจ ื”ื’ื ื•ื" P53) ื•ืฉื•ืœื— ืื•ืชื• ืœืคื™ืจื•ืง ืžื”ื™ืจ, ืžื“ื“ื™ื• ื™ื•ืจื“ื™ื [ืžืงื•ืจ1, ืžืงื•ืจ2].

ื‘ืชืื™ื ืชืงื™ื ื™ื (ืœื ืกืจื˜ื ื™ื™ื), ื”ืงื™ืฉื•ืจ ื‘ื™ืŸ MDM2 ืœ-p53 ืื™ื ื• ื ืฉื‘ืจ ื‘ื“ืจืš ื›ืœืœ; ืœื”ื™ืคืš, MDM2 ื ืงืฉืจ ืœ-p53 ื•ืžืขื›ื‘ ืื•ืชื• ื‘ืื•ืคืŸ ืคืขื™ืœ, ื•ื‘ื›ืš ืฉื•ืžืจ ืขืœ ืจืžื•ืช p53 ื ืžื•ื›ื•ืช ื•ืžื•ื ืข ื”ืคืขืœื” ืžื™ื•ืชืจืช ืฉืœ ืžื•ื•ืช ืชืื™. ื”ืงืฉืจ ื ืฉื‘ืจ ื•-p53 ื”ื•ืคืš ืœืคืขื™ืœ ืจืง ื›ืืฉืจ ื”ืชื ื—ื•ื•ื” ืขืงื” (Stress), ื›ื’ื•ืŸ ื ื–ืง ืœ-DNA [ืžืงื•ืจ].

ื‘ืขืงื‘ื•ืช ื ื–ืง ืœ-DNA: ืื ื–ื™ืžื™ื (ื›ืžื• ATM) ืžื–ืจื—ื ื™ื (phosphorylate) ืืช p53 ื•-MDM2. ื”ืชื•ืฆืื” ืžื›ืš ืฉื”ื–ืจื—ื•ืŸ ืžื•ื ืข ืืช ื”ื™ื›ื•ืœืช ืฉืœ MDM2 ืœื”ื™ืงืฉืจ ืœ-p53. ื‘ืชืื™ื ืกืจื˜ื ื™ื™ื, ืžื ื’ื ื•ืŸ ื–ื” ืžืฉื•ื‘ืฉ, ืœืขื™ืชื™ื ืงืจื•ื‘ื•ืช ื‘ืฉืœ ืขื•ื“ืฃ MDM2 ื”ืžื•ื ืข ืž-p53 ืœืคืขื•ืœ, ืžื” ืฉื”ื•ืคืš ืืช ื”ืฉื‘ื™ืจื” ื”ืžืœืื›ื•ืชื™ืช ืฉืœ ืงืฉืจ ื–ื” ืœืžื•ื˜ื™ื‘ ืชื—ืœื•ืื” [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3].

ื‘ืžืงื‘ื™ืœ ืคื•ืขืœื™ื ื‘ื’ื•ืฃ ื”ืื“ื ืžืกืœื•ืœื™ื ืžืฉืœื™ืžื™ื ืฉืœ ื”ื—ืœืžื”:- **AMPK** โ€“ ื—ื™ื™ืฉืŸ ื”ืื ืจื’ื™ื”, ืฉืžืขื•ื“ื“ ืชื™ืงื•ืŸ ื•ื”ืคื—ืชืช ืฆืจื™ื›ื”.- **SIRT1**, **PGC-1ฮฑ**, **FOXO**, **Nrf2** ื•-**TFEB** โ€“ ืฉืชื•ืžื›ื™ื ื‘ื ื™ืงื•ื™ ืชืื™, ืฉืจื™ืคืช ืฉื•ืžื ื™ื, ื™ืฆื™ืจืช ืžื™ื˜ื•ื›ื•ื ื“ืจื™ื•ืช ื—ื“ืฉื•ืช ื•ื”ื’ื ื” ืžืคื ื™ ืžืชื— ื—ืžืฆื•ื ื™.- ืœืขื•ืžืชื, ืฆื™ืจ **PI3KAktmTOR** ืžืงื“ื ื‘ื ื™ื™ื” ืจืฆื™ืคื”, ืืš ื›ืฉื”ื•ื ืคืขื™ืœ ืžื“ื™ (ื‘ื’ืœืœ ืชื–ื•ื ื” ืฉื’ื•ื™ื”) ื”ื•ื ืžืคืจื™ืข ืœ-p53 ื•ืžืงืฉื” ืขืœ ื”ื”ืฉืชื”ื•ืช ื•ื”ืชื™ืงื•ืŸ.

ื›ืžื• **ืขื•ืฃ ื”ื—ื•ืœ ๐Ÿฆโ€๐Ÿ”ฅ** ืฉื‘ืžื™ืชื•ืก โ€“ ื”ืชื ื ื•ืชืŸ ืœ"ืืฉ" (ื”ืžืชื—) ืœืขืฉื•ืช ืืช ืฉืœื”, ื ืฉืจืฃ ื‘ืื•ืคืŸ ืžื‘ื•ืงืจ, ื•ืžืชื—ื“ืฉ ื•ืžืชืงื‘ืœ ืžืฆื‘ ื—ื–ืง ื™ื•ืชืจ. ื”ื”ืฉืชื”ื•ืช ื”ื‘ื™ื•ืœื•ื’ื™ืช ืžืจืชืงืช, ื”ื™ื ื™ืฆื™ืจื” ืฉืœ ื”ื˜ื‘ืข, ื•ืื™ื ื” ื—ื•ืœืฉื”, ืื•ืœ ื”ื™ื ืจืžื– ืœ **ื—ื•ื›ืžื” ื‘ื™ื•ืœื•ื’ื™ืช** ืœื—ื•ื›ืžืช ื”ื™ืงื•ื, ืœื™ื›ื•ืœืช ืฉืฉื•ืžืจืช ืขืœ ื™ืฆื™ื‘ื•ืช ื”ื’ื ื•ื ื•ืขืœ ื‘ืจื™ืื•ืช ืืจื•ื›ืช ื˜ื•ื•ื— [ืžืงื•ืจ1, ืžืงื•ืจ2].

ื›ื™ืฆื“ P53 ืคื•ืขืœโ“

ื›ืืฉืจ ื—ืœื‘ื•ืŸ p53 (ื”ืžื›ื•ื ื” "ืฉื•ืžืจ ื”ื’ื ื•ื") ืžื–ื”ื” ื ื–ืง ื‘-DNA, ื”ื•ื ืคื•ืขืœ ื‘ืžื ื’ื ื•ืŸ ื“ื•-ืฉืœื‘ื™ ืžื“ื•ื™ืง ืฉื ื•ืขื“ ืœืฉืžื•ืจ ืขืœ ืชืงื™ื ื•ืช ื”ืชื ื•ืžื ืกื” ืœืขืฆื•ืจ, ื‘ืชืงื•ื” ืœืžื ื•ืข ืกืจื˜ืŸ

[ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3, ืžืงื•ืจ4].

1. ื”ืฉื”ื™ื” (Cell Cycle Arrest)

ื›ื“ื™ ืœืžื ื•ืข ืžื”ืชื ืœืฉื›ืคืœ DNA ืคื’ื•ื ื•ืœื”ืขื‘ื™ืจื• ื”ืœืื”, p53 ืขื•ืฆืจ ืืช "ืžื—ื–ื•ืจ ื”ืชื": [ืžืงื•ืจ1, ืžืงื•ืจ2]

  • ื”ืคืขืœืช p21: ื—ืœื‘ื•ืŸ p53 ืคื•ืขืœ ื›ื’ื•ืจื ืฉืขืชื•ืง ื•ืžืคืขื™ืœ ืืช ื”ื’ืŸ ื”ืžื™ื™ืฆืจ ืืช ื”ื—ืœื‘ื•ืŸ p21.
  • ืขืฆื™ืจืช ื”ืžื ื•ืข ื”ืชืื™: ื—ืœื‘ื•ืŸ p21 ื ืงืฉืจ ืœืื ื–ื™ืžื™ื (CDKs) ืฉืื—ืจืื™ื ืขืœ ื”ืชืงื“ืžื•ืช ืžื—ื–ื•ืจ ื”ืชื ื•ืžื ื˜ืจืœ ืื•ืชื.
  • ื”ืชื•ืฆืื”: ื”ืชื ื ืขืฆืจ ื‘ื ืงื•ื“ืช ื‘ื™ืงื•ืจืช (ื‘ื“ืจืš ื›ืœืœ ื‘ืฉืœื‘ G1), ืžื” ืฉืžืขื ื™ืง ืœื• ืืช "ื”ื–ืžืŸ" ื”ื“ืจื•ืฉ ืœื‘ื“ื™ืงื” ื•ืชื™ืงื•ืŸ ืœืคื ื™ ื”ื—ืœื•ืงื”. [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3, ืžืงื•ืจ4, ืžืงื•ืจ5].
  • ื”ืื“ื ื ื“ืจืฉ ืื– ืœืคืขื•ืœ ื‘ืื•ืชื• ืื•ืคืŸ, ืื‘ืœ ืื™ืŸ ืœืฉื•ืžืจ ื”ื’ื ื•ื ืฉื•ื ื”ืฉืคืขื” ืขืœ ื”ืžื—ืฉื‘ื” ื”ืื ื•ืฉื™ืช, ืขืœ ื”ื”ื—ืœื˜ื•ืช ื•ืขืœ ื”ืชืื‘ื•ืช.

2. ื”ืคืขืœืช ืžื ื’ื ื•ื ื™ ืชื™ืงื•ืŸ (DNA Repair)

ื‘ื–ืžืŸ ืฉื”ืชื ื ืžืฆื ื‘"ื”ืฉื”ื™ื”", p53 ื“ื•ืื’ ืœืชื™ืงื•ืŸ ื”ื ื–ืง ื‘ืื•ืคืŸ ืืงื˜ื™ื‘ื™: [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3]

  • ื’ื™ื•ืก ืฆื•ื•ืชื™ ืชื™ืงื•ืŸ: p53 ืžืขื•ืจืจ ืฉืขืชื•ืง ืฉืœ ื’ื ื™ื ื”ืžืงื•ื“ื“ื™ื ืœื—ืœื‘ื•ื ื™ื ื”ืžืชืžื—ื™ื ื‘ืชื™ืงื•ืŸ DNA, ื›ืžื• ื—ืœื‘ื•ื ื™ื ืžืžืฉืคื—ืช GADD45.
  • ืกื•ื’ื™ ืชื™ืงื•ืŸ: ื”ื•ื ืžืคืขื™ืœ ืžืขืจื›ื•ืช ืฉื•ื ื•ืช ื‘ื”ืชืื ืœืกื•ื’ ื”ื ื–ืง, ื›ื•ืœืœ ืชื™ืงื•ืŸ ืฉื‘ืจื™ื ื‘-DNA ื•ืชื™ืงื•ืŸ ื˜ืขื•ื™ื•ืช ื‘ื‘ืกื™ืกื™ ื”-DNA (ื›ืžื• ืžื ื’ื ื•ื ื™ NER ื•-BER) [ืžืงื•ืจ].
  • ื”ื”ื›ืจืขื”: ืื ื”ืžื ื’ื ื•ื ื™ื ืžืฆืœื™ื—ื™ื ืœืชืงืŸ ืืช ื”ื ื–ืง, p53 "ืžืฉื—ืจืจ" ืืช ื”ืขืฆื™ืจื” ื•ื”ืชื ืžืžืฉื™ืš ื‘ื—ืœื•ืงื”. ืื ื”ื ื–ืง ื—ืžื•ืจ ืžื“ื™ ื•ืื™ื ื• ื ื™ืชืŸ ืœืชื™ืงื•ืŸ, p53 ื™ืคืขื™ืœ ืžืกืœื•ืœ ืฉืœ ืžื•ื•ืช ืชืื™ ืžืชื•ื›ื ืŸ (ืืคื•ืคื˜ื•ื–ื™ืก) ื›ื“ื™ ืœื”ืฉืžื™ื“ ืืช ื”ืชื ื”ืคื’ื•ื. [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3, ืžืงื•ืจ4, ืžืงื•ืจ5, ืžืงื•ืจ6, ืžืงื•ืจ7].
  • ืžื”ืœื›ื™ื ืืœื• ืœื ืžืชืงื™ื™ืžื™ื ื‘ืžื•ื˜ืฆื™ื” ื›ืืฉืจ ื”ืžื ื’ื ื•ืŸ ืฉืœ ื”P53 ื ืคื’ืข.

ืžื” ืงื•ืจื” ื›ืืฉืจ ืžื ื’ื ื•ืŸ ื”-p53 ื ืคื’ื ื•ืื™ื ื• ืžืฆืœื™ื— ืœื‘ืฆืข ืืช ื”ืขืฆื™ืจื” ื”ื–ื•

ื›ืืฉืจ ืžื ื’ื ื•ืŸ ื”-p53 ื ืคื’ื (ื‘ื“ืจืš ื›ืœืœ ืขืงื‘ ืžื•ื˜ืฆื™ื” ื’ื ื˜ื™ืช), ื”ืชื ืžืื‘ื“ ืืช ื”"ื‘ืœืžื™ื" ืฉืœื• ื•ืืช ื™ื›ื•ืœืช ื”ื‘ื™ืงื•ืจืช. ื”ืชื•ืฆืื” ื”ื™ื ืฉืจืฉืจืช ืื™ืจื•ืขื™ื ื”ืจืกื ื™ืช:

  1. ืื•ื‘ื“ืŸ ื”"ืกืงื•ืœื”" (ื”ื”ืฉืชื”ื•ืช): ื”ืชื ืื™ื ื• ืขื•ืฆืจ ื‘ื ืงื•ื“ื•ืช ื”ื‘ื™ืงื•ืจืช. ื’ื ืื ื”-DNA ืคื’ื•ื, ื”ืชื ืžืžืฉื™ืš ืœื”ืฉืชื›ืคืœ ืœืœื ื”ืคืกืงื”. ื–ื”ื• ืžืฆื‘ ืฉืœ "ืจื™ืฆื” ืขื™ื•ื•ืจืช".
  2. ื”ืฆื˜ื‘ืจื•ืช ืžื•ื˜ืฆื™ื•ืช: ืžื›ื™ื•ื•ืŸ ืฉืžื ื’ื ื•ื ื™ ื”ืชื™ืงื•ืŸ ืœื ื”ื•ืคืขืœื•, ื˜ืขื•ื™ื•ืช ื”ื”ืขืชืงื” ื”ื•ืคื›ื•ืช ืœืงื‘ื•ืขื•ืช. ื›ืœ ื“ื•ืจ ื—ื“ืฉ ืฉืœ ืชืื™ื ื ื•ืฉื ื™ื•ืชืจ "ืฉื’ื™ืื•ืช ื›ืชื™ื‘" ื’ื ื˜ื™ื•ืช ืžืงื•ื“ืžื•.
  3. ื”ืชื—ืžืงื•ืช ืžืžื•ื•ืช ืชืื™: ื‘ืžืฆื‘ ืชืงื™ืŸ, ืชื ืคื’ื•ื ืžืื•ื“ ืืžื•ืจ ืœื”ืชืื‘ื“ (ืืคื•ืคื˜ื•ื–ื™ืก). ื›ืฉ-p53 ืคื’ื•ื, ื”ืคืงื•ื“ื” ื”ื–ื• ืœื ื ื™ืชื ืช, ื•ื”ืชื ื”ื•ืคืš ืœ"ืืœืžื•ืชื™" ื‘ืžื•ื‘ืŸ ื”ืฉืœื™ืœื™ โ€“ ื”ื•ื ืžืžืฉื™ืš ืœื—ื™ื•ืช ื•ืœืฉื’ืฉื’ ืœืžืจื•ืช ื”ื™ื•ืชื• ืคื’ื•ื ื•ืžืกื•ื›ืŸ.
  4. ื”ืชืคืชื—ื•ืช ืกืจื˜ืŸ: ื”ืฉื™ืœื•ื‘ ืฉืœ ื—ืœื•ืงื” ืžื”ื™ืจื”, ื—ื•ืกืจ ืชื™ืงื•ืŸ ื•ืื™-ื™ื›ื•ืœืช ืœืžื•ืช ืžื•ื‘ื™ืœ ืœื™ืฆื™ืจืช ื’ื™ื“ื•ืœ ืžืžืื™ืจ. ืœืžืขืฉื”, ืžื•ื˜ืฆื™ื•ืช ื‘ื—ืœื‘ื•ืŸ p53 ื ืžืฆืื•ืช ื‘ื›-50% ืžื›ืœืœ ืกื•ื’ื™ ื”ืกืจื˜ืŸ ื‘ื‘ื ื™ ืื“ื [ืžืงื•ืจ].

ื‘ื ืžืฉืœ ื”ืชื•ื“ืขืชื™ ืฉืœื ื•: ืื“ื ืฉืžืื‘ื“ ืืช ื™ื›ื•ืœืช ื”-p53 ืฉืœื• ื”ื•ื ืื“ื ืฉืจืฅ ื‘ื—ื™ื™ื ืžื‘ืœื™ ืœืขืฆื•ืจ ื•ืœื‘ื—ื•ืŸ ื˜ืขื•ื™ื•ืช. ื”ื•ื ืœื ืžืฉืชื”ื”, ืื™ืŸ ืชื•ื“ืขื” ืขืฆืžื™ืช, ื”ื•ื ืœื ืžืงืฉื™ื‘ ืœืืžืช, ื•ื—ื•ื–ืจ ืขืœ ืื•ืชืŸ ืฉื’ื™ืื•ืช, ืฆื•ื‘ืจ "ื ื–ืงื™ื" ื ืคืฉื™ื™ื ืื• ืžืงืฆื•ืขื™ื™ื, ื•ืื™ื ื• ืžืกื•ื’ืœ ืœื‘ืฆืข ืชื™ืงื•ืŸ (Refinement), ืžื” ืฉืžื•ื‘ื™ืœ ื‘ืกื•ืคื• ืฉืœ ื“ื‘ืจ ืœืงืจื™ืกืช ื”ืžืขืจื›ืช ื”ืื™ืฉื™ืช ืฉืœื•.

ื›ืืŸ ืฉื‘ื” ื•ืžื”ื“ื”ื“ืช ืื—ืช ื”ืฉืืœื•ืช ื”ืžืจืชืงื•ืช ื ื•ื›ื— ืžื—ืœื” ื”ื•ืจื’ืช ืฉืžืงื•ืจื•ืชื™ื” ืคืขืžื™ื ืจื‘ื•ืช ื”ืฉื™ื ื•ื™ (ื”ืžื•ื˜ืฆื™ื”) ืฉ"ืฉื•ืžืจ ื”ื’ื ื•ื" (the" โ€œguardian of the genome) p53 ๐Ÿฆโ€๐Ÿ”ฅ ืขื•ื‘ืจ, ื•ืžืฉืชืชืง ื‘ื’ืœืœื”, ืœื ืžืฉืชื”ื”, ืืœื ืงื•ืจืก, ื ืขื“ืจ ื•ื”ื•ืคืš ืคืกื™ื‘ื™ ื•ืœื ืคืขื™ืœ ื›ืคื™ ืฉืงื•ืจื” ื‘ืจื•ื‘ ื”ื’ื™ื“ื•ืœื™ื ื”ืžืžืื™ืจื™ื [ืžืงื•ืจ].
ื›ื™ืฆื“ ื”ืฉื•ืžืจ ืฉื”ื˜ื‘ืข ื”ืขื ื™ืง ืœื ื• ื ื”ืจืก ื“ื•ื•ืงื ื›ืฉืื ื—ื ื• ื”ื›ื™ ื ื“ืจืฉื™ื ืœืขื–ืจืชื•โ“[ืžืงื•ืจ].
ืื‘ืœ ื”ืงืจื™ืกื” ื”ื–ื• ืื™ื ื” ืžืชืจื—ืฉืช ื‘ื—ืœืœ ืจื™ืง.
ื”ื™ื ืชืœื•ื™ื” ื‘ืกื‘ื™ื‘ื” โ€”
ื‘ืจืžื•ืช ื”ืื ืจื’ื™ื”, ื‘ืขื•ืžืก ื”ื—ืžืฆื•ื ื™, ื‘ืžื” ืฉื ื›ื ืก ืœื’ื•ืฃ ื™ื•ื ืื—ืจื™ ื™ื•ื.
ื•ื™ืฉ ืจื’ืขื™ื ืฉื‘ื”ื ืฉื™ื ื•ื™ ืžื“ื•ื™ืง โ€”
ื‘ืžื–ื•ืŸ, ื‘ืขื•ืžืก, ื‘ืงืฆื‘ โ€”
ืœื โ€œืžืชืงืŸโ€ ืื•ืœื™ ืืช ื”ืžื•ื˜ืฆื™ื”,
ืื‘ืœ ื›ืŸ ืžืฉื ื” ืืช ืฉื“ื” ื”ืงืจื‘ ืฉื‘ื• ื”ื™ื ืคื•ืขืœืช [ืžืงื•ืจ].
ื•ื”ืฉืืœื” ื›ื‘ืจ ืื™ื ื” ืจืง ื›ื™ืฆื“ ืžืขืจื›ืช ื”ื”ื’ื ื” ืงืจืกื” โ€”
ืืœื ื”ืื ื ื™ืชืŸ ืœื”ื—ื–ื™ืจ ืœืชืื™ื ืืช ื”ืชื ืื™ื ืฉื‘ื”ื ืฉื•ืžืจ ื”ื’ื ื•ื ืฉื•ื‘ ื™ืคืขืœ.

ื›ืฉืื ื• ืžื“ื™ื™ืงื™ื ืืช ื”ืชื–ื•ื ื” ื”ืžื—ืœื™ืžื”, ืื ื• ืžืืคืฉืจื™ื ืœ-p53 ื•ืœืžืกืœื•ืœื™ ื”ื”ื—ืœืžื” ืœืขืงื•ืฃ ืืช ื”ื ื–ืง ืฉืžืชืจื—ืฉ ืœื”ื•ื‘ื™ืœ, ืœืขื‘ื•ื“ ื‘ื™ืขื™ืœื•ืช โ€“ ื•ืœื—ื“ืฉ ืืช ื›ื•ื—ื•ืช ื”ื”ื—ืœืžื” [ืžืงื•ืจ], ื›ื•ืœืœ ืืช ื”ื”ืชื‘ื•ื ื ื•ืช ื”ืคื ื™ืžื™ืช, ืœื‘ืงืฉ ืืช ื”ืขืฆื” ื”ื˜ื•ื‘ื”, ืื•ืœื™ ื“ื•ื•ืงื ืขื›ืฉื™ื• ื”ื”ืฉื”ื™ื” ืชืกื™ื™ืข ืœ"ืื•ื”ื‘ื™ ื”ื‘ื“ื•ื™ื•ืช, ืกื™ืกืžืื•ืช ื”ื›ื–ื‘, ืกื•ื’ื“ื™ ื”ืœื ืงื™ื™ื" , ื•ืื•ื”ื‘ื™ ื”ื‘ื˜ื—ื•ืช ื”ืฉื•ื•ื ืœื”ืคื•ืš ืขืฆื™ืจื” ืฉื”ื™ืชื” ืžื—ืœื•ื ื ื”ื ืชื ื•ืช ืœื’ื™ื”ื ื•ื, ืœืืชื ื—ืชื ื•ื‘ื”ืžืฉืš ื’ื ืื•ืœื™ ืœื”ืชื—ื“ืฉื•ืช ืืžื™ืชื™ืช ืžื‘ื•ืกืกืช ื™ื“ื™ืขื” ื ื›ื•ื ื” ืฉืชื•ื‘ื™ืœ ืœื‘ื ื™ื” [ืžืงื•ืจ1, ืžืงื•ืจ2].

p53 ื”ื•ื ื—ืœื‘ื•ืŸ ืžืคืชื— ืฉืžื•ื ืข ื”ืฆื˜ื‘ืจื•ืช ื ื–ืงื™ DNA, ืžืขื•ื“ื“ ืชื™ืงื•ืŸ DNA, ืขืฆื™ืจืช ืžื—ื–ื•ืจ ืชื ืื• ืืคื•ืคื˜ื•ื–ื™ืก (ืžื•ื•ืช ืชืื™ ืžืชื•ื›ื ืช) ื‘ืชืื™ื ืคื’ื•ืžื™ื. ืงื™ืคื•ืœ ืœื ืชืงื™ืŸ (Unfolded p53): ืฉืœ ื”-p53 ืžืฉื ื” ืืช ืฆื•ืจืชื• ื”ืžืจื—ื‘ื™ืช (ืงื•ื ืคื•ืจืžืฆื™ื”) ื•ื”ื•ืคืš ืื•ืชื• ืœื‘ืœืชื™ ืชืงื™ืŸ. ืฉื™ื ื•ื™ ื–ื” (ืžื•ื˜ืฆื™ื”) ื’ื•ืจื ืœื• ืœืื‘ื“ ืืช ื™ื›ื•ืœืชื• ืœื”ื’ืŸ ืขืœ ื”ื—ื•ืžืจ ื”ื’ื ื˜ื™ ื‘ืžื—ืœื•ืช ื›ืจื•ื ื™ื•ืช ืงืฉื•ืช, ื’ื ืขืœ ืชืื™ ื”ืขืฆื‘. ื”ื•ื ืœืžืฉืœ ื”ืขื•ืžื“ ืžืื—ื•ืจื™ ื”ืงืœืขื™ื ืฉืœ ืžื—ืœืช ื”ืืœืฆื”ื™ื™ืžืจ. ืžืจื’ืข ืฉืฉื•ืžืจ ื”ื’ื ื•ื ื”ื•ืคืš ืœืฉื˜ืŸ ืฉืœื• ื”ื•ื ืžืชื—ื™ืœ ืœืขื•ื“ื“ ืชื”ืœื™ื›ื™ื ื“ืœืงืชื™ื™ื ื•ืžื•ื•ืช ืชืื™ (ืืคื•ืคื˜ื•ื–ื™ืก) ื‘ืžื•ื—.

ืžื•ื˜ืฆื™ื•ืช ื‘-p53 ื ืคื•ืฆื•ืช ืžืื•ื“ ื‘ืกืจื˜ืŸ (~50% ืžื”ื’ื™ื“ื•ืœื™ื), ื•ื”ื’ืจืกื” ื”ืžื•ื˜ื ื˜ื™ืช ืžืื‘ื“ืช ืืช ืชืคืงื™ื“ื” ื”ืžื’ืŸ ื•ืœืขื™ืชื™ื, ื›ืืžื•ืจ ืœืขื™ืœ, ื’ื ื›ืืŸ ื”ื™ื ืžืงื‘ืœืช Gain-of-Function (GOF) โ€“ ืคืขื™ืœื•ื™ื•ืช "ืจืขื•ืช" ืฉืžืงื“ืžื•ืช ื’ื™ื“ื•ืœ, ื’ืจื•ืจื•ืช, ื™ืฆื™ืจืช ื›ืœื™ ื“ื (ืื ื’ื™ื•ื’ื ื–ื”) ื•ืขืžื™ื“ื•ืช ืœื›ื™ืžื•ืชืจืคื™ื” [ืžืงื•ืจ].

ื”ืฉืคืขื•ืช ืฉืœ ืชื–ื•ื ื” ืขืฉื™ืจื” ื‘ืฉื•ืžืŸ ืžื”ื—ื™, (ืฉื•ืžืŸ ืจื•ื•ื™ ื•ืฉื•ืžืŸ ื˜ืจื ืก) ื’ื ื›ื•ืœืกื˜ืจื•ืœ ืขืœ p53

ืขื•ื“ืฃ ืœื™ืคื™ื“ื™ื (ืฉื•ืžื ื™ื) ื•ื›ื•ืœืกื˜ืจื•ืœ ื™ื›ื•ืœ ืœื™ื™ืฆื‘ ื’ืจืกืื•ืช ืžื•ื˜ื ื˜ื™ื•ืช ืฉืœ p53 ื“ืจืš ื ืชื™ื‘ ื”ืžื•ื•ืœื•ื ื˜ (mevalonate pathway). ืžื•ื˜ื ื˜ื™ p53 ืžืฉืชืคื™ื ืคืขื•ืœื” ืขื ื’ื•ืจืžื™ ืฉื™ืขืชื•ืง ื›ืžื• SREBP, ืžื” ืฉืžื’ื‘ื™ืจ ื™ื™ืฆื•ืจ ื›ื•ืœืกื˜ืจื•ืœ ื•ืœื™ืคื™ื“ื™ื โ€“ ื•ื™ื•ืฆืจ ืœื•ืœืืช ืžืฉื•ื‘ ื—ื™ื•ื‘ื™ืช ืฉืžืงื“ืžืช ืฆืžื™ื—ืช ื’ื™ื“ื•ืœ [ืžืงื•ืจ]. ืžื—ืงืจื™ื ืžืจืื™ื ืฉืชื–ื•ื ื” ืขืฉื™ืจื” ื‘ืฉื•ืžืŸ ืจื•ื•ื™ (ื—ืžืื”, ื’ื‘ื™ื ื•ืช, ื‘ืฉืจ ืื“ื•ื, ื‘ื™ื™ืงื•ืŸ, ืžื–ื•ืŸ ืžืขื•ื‘ื“) ืงืฉื•ืจื” ืœื”ืฆื˜ื‘ืจื•ืช ื˜ื™ืคื•ืช ืฉื•ืžืŸ (Lipid Droplets) ื‘ืชืื™ ื’ื™ื“ื•ืœ. ื˜ื™ืคื•ืช ืืœื• ื™ื›ื•ืœื•ืช ืœืืจื’ืŸ ืคื™ืจื•ืง ืžื”ื™ืจ ื™ื•ืชืจ ืฉืœ p53 ื”ืชืงื™ืŸ ื“ืจืš MDM2, ืžื” ืฉืžื—ืœื™ืฉ ืืช ื”ื”ื’ื ื” [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3, ืžืงื•ืจ4].

ืกื•ื›ืจ ื•ื’ืœื•ืงื•ื– ื’ื‘ื•ื”ื™ื โ€” ืขื•ืžืก ื’ืœื™ืงืžื™ ื’ื‘ื•ื” ืขืœื•ืœ ืœื”ื—ืžื™ืจ ื ื–ืง ื—ืžืฆื•ื ื™ ื•ืœืชืจื•ื ืœืžื•ื˜ืฆื™ื•ืช. ื”ื’ื‘ืœืช ืคื—ืžื™ืžื•ืช/ืกื•ื›ืจื™ื ืขืฉื•ื™ื” ืœืฉืคืจ ื™ืฆื™ื‘ื•ืช p53 ื•ืœืขื•ื“ื“ ืคื™ืจื•ืง ืฉืœ ื”ื’ืจืกื” ื”ืžื•ื˜ื ื˜ื™ืช [ืžืงื•ืจ1, ืžืงื•ืจ2].

ื—ื•ืกืจ ื ื•ื’ื“ื™ ื—ืžืฆื•ืŸ โ€” ืชื–ื•ื ื” ื“ืœื” ื‘ื™ืจืงื•ืช ื•ืขื•ื“ืฃ ืคื™ืจื•ืช ืžื’ื‘ื™ืจื” ืขืงื” ื—ืžืฆื•ื ื™ืช (ROS), ืฉืคื•ื’ืขืช ื‘-p53.

p53 ื‘ืืœืฆื”ื™ื™ืžืจ

ื‘ืืœืฆื”ื™ื™ืžืจ ืžืชืจื—ืฉ ืฉื™ื ื•ื™ ืงื•ื ืคื•ืจืžืฆื™ื•ื ื™ (Unfolded p53 ืื• U-p53) โ€“ ื”ื—ืœื‘ื•ืŸ "ืžืชืคืจืง" ืฆื•ืจื ื™ืช, ืžืื‘ื“ ืชืคืงื•ื“ ืžื’ืŸ ื•ืžืงื“ื ื“ืœืงืช ื•ืžื•ื•ืช ืชืื™ ื‘ืžื•ื—. ืฉื™ื ื•ื™ ื–ื” ื ื™ืชืŸ ืœื–ื™ื”ื•ื™ ื‘ื“ื ื•ื‘ืชืื™ื ื”ื™ืงืคื™ื™ื ื›ื‘ืจ ื‘ืฉืœื‘ื™ื ืžื•ืงื“ืžื™ื (ืœืคื ื™ ืชืกืžื™ื ื™ ื–ื™ื›ืจื•ืŸ).

ืขื“ื•ื™ื•ืช ื—ื“ืฉื•ืช ืžืœืžื“ื•ืช ืขืœ ื›ืš ืฉื—ืœื‘ื•ื ื™ื ืžื–ื™ืงื™ื (ื›ืžื• -ฮฒ ื•ื’ื•ืจืžื™ื-ืขืžื™ืœื•ืื™ื“) ืขืฉื•ื™ื™ื ืœื”ื™ื•ื•ืฆืจ ื‘ืžืขื™ื™ื ื•ืœื ื“ื•ื“ ืืœ ื”ืžื•ื— ื“ืจืš ืขืฆื‘ ื”ื•ื•ืื’ื•ืก.

ื‘ื”ืงืฉืจ ื–ื” ื”ืื ื”ืจื•ืคื ื”ืžื˜ืคืœ ื›ื‘ืจ ื”ืžืœื™ืฅ ืœืš ืขืœ ืกื˜ื˜ื™ื ื™ื โ“

ืกื˜ื˜ื™ื ื™ื (ืœื”ื•ืจื“ืช ื›ื•ืœืกื˜ืจื•ืœ) โ€” ื‘ืžืคืชื™ืข, ื”ื ื™ื›ื•ืœื™ื ืœืงื“ื ืคื™ืจื•ืง ืฉืœ p53 ืžื•ื˜ื ื˜ื™ (ื‘ืžื™ื•ื—ื“ conformational mutants).

ืœืžืืžืจื™

ืขืœ ื›ืš ื‘ื”ืžืฉืš.

ืžื” ืงื•ืจื” ืขื P53 ื‘ืกืจื˜ืŸ?

ื‘ืกืจื˜ืŸ, ืžื•ื˜ืฆื™ื•ืช ื‘ื’ืŸ TP53 (ืฉืžืงื•ื“ื“ ืœ-p53) ืžืชืจื—ืฉื•ืช ื‘ื›-50% ืžื”ื’ื™ื“ื•ืœื™ื ื”ืื ื•ืฉื™ื™ื (ื•ืœืขื™ืชื™ื ืงืจื•ื‘ื•ืช ื™ื•ืชืจ ื‘ืกื•ื’ื™ื ืžืกื•ื™ืžื™ื ื›ืžื• ืกืจื˜ืŸ ืฉื“, ืžืขื™ ื’ืก, ืจื™ืื•ืช, ืฉื—ืœื•ืช ื•ืขื•ื“). ืจื•ื‘ ื”ืžื•ื˜ืฆื™ื•ืช ื”ืŸ missense mutations ื‘ืื–ื•ืจ ื”-DNA-binding domain (DBD), ื‘ืขื™ืงืจ ื‘"ื ืงื•ื“ื•ืช ื—ืžื•ืช" (hotspots) ื›ืžื• R175, R248, R273 ื•ื›ื•'.

ื”ื—ื•ืงืจื™ื ืžื“ื•ื•ื—ื™ื ืขืœ ืฉื ื™ ืกื•ื’ื™ื ืขื™ืงืจื™ื™ื ืฉืœ ืžื•ื˜ืฆื™ื•ืช ื›ืืœื”:

  • Contact mutations โ€” (ื›ืžื• R273H, R248Q): ื”ื—ืœื‘ื•ืŸ ืฉื•ืžืจ ืขืœ ืžื‘ื ื” ื›ืœืœื™ ื™ื—ืกื™ืช, ืื‘ืœ ืžืื‘ื“ ื™ื›ื•ืœืช ืœืงืฉื•ืจ DNA ื‘ืฆื•ืจื” ืกืคืฆื™ืคื™ืช.
  • Conformational / structural mutations โ€” (ื›ืžื• R175H, Y220C, R249S): ื”ืžื•ื˜ืฆื™ื” ื’ื•ืจืžืช ืœืฉื™ื ื•ื™ ืงื•ื ืคื•ืจืžืฆื™ื•ื ื™ ืžืฉืžืขื•ืชื™ โ€“ ื”ื—ืœื‘ื•ืŸ ื”ื•ืคืš ืœ"ืœื ื™ืฆื™ื‘" ื™ื•ืชืจ, "ืžืชืคืจืง" ื—ืœืงื™ืช (misfolded/unfolded), ื•ืžืื‘ื“ ืืช ื”ืžื‘ื ื” ื”ืชืงื™ืŸ ืฉืœื•. ื–ื” ื“ื•ืžื” ื‘ืžื•ื‘ืŸ ืžืกื•ื™ื ืœ"Unfolded p53" ืฉืชื™ืืจืช ื‘ืืœืฆื”ื™ื™ืžืจ, ืื‘ืœ ืขื ื”ื‘ื“ืœ ื—ืฉื•ื‘: ื‘ืกืจื˜ืŸ ื–ื” ืงืฉื•ืจ ื‘ื“ืจืš ื›ืœืœ ืœืžื•ื˜ืฆื™ื” ื’ื ื˜ื™ืช ื™ืฉื™ืจื”.

ื”ื”ืฉืคืขื•ืช ื”ืขื™ืงืจื™ื•ืช ื‘ืกืจื˜ืŸ:

  1. Loss of Function (LOF) โ€” ื”-p53 ื”ืชืงื™ืŸ ("ืฉื•ืžืจ ื”ื’ื ื•ื") ืžืื‘ื“ ืืช ื™ื›ื•ืœืชื•:
  • ืœื–ื”ื•ืช ื ื–ืงื™ DNA.
  • ืœืขืฆื•ืจ ืžื—ื–ื•ืจ ืชื.
  • ืœืชืงืŸ DNA.
  • ืœื”ืคืขื™ืœ ืืคื•ืคื˜ื•ื–ื™ืก (ืžื•ื•ืช ืชืื™ ืžืชื•ื›ื ืช) ื‘ืชืื™ื ืคื’ื•ืžื™ื.
    โ†’ ืชืื™ื ืขื ื ื–ืง ื’ื ื˜ื™ ืžืžืฉื™ื›ื™ื ืœื”ืชื—ืœืง ืœืœื ื‘ืงืจื”.
  1. Dominant-Negative Effect โ€” ื”ื—ืœื‘ื•ืŸ ื”ืžื•ื˜ื ื˜ื™ ื™ื›ื•ืœ "ืœื”ืจืขื™ืœ" ืืช ื”ืขื•ืชืง ื”ืชืงื™ืŸ ืฉื ื•ืชืจ (ืื ื™ืฉ ื›ื–ื”) ืขืœ ื™ื“ื™ ื™ืฆื™ืจืช ื˜ื˜ืจืืžืจื™ื ืœื ืชืงื™ื ื™ื.
  2. Gain-of-Function (GOF) โ€“ "ื”ืคื™ื›ื” ืœืฉื˜ืŸ" โ€” ื–ื” ื”ื—ืœืง ื”ื“ืจืžื˜ื™ ื‘ื™ื•ืชืจ:
  • ื”ื—ืœื‘ื•ืŸ ื”ืžื•ื˜ื ื˜ื™ p53 (ื‘ืžื™ื•ื—ื“ ื›ืฉื”ื•ื ืžืฆื˜ื‘ืจ ื‘ืจืžื•ืช ื’ื‘ื•ื”ื•ืช ื‘ืชื) ืžืงื‘ืœ ืชืคืงื™ื“ื™ื ื—ื“ืฉื™ื ื•ืžื–ื™ืงื™ื ืฉืื™ืŸ ืœื• ื‘-wild-type.
  • ื”ื•ื ืžืฉืชืฃ ืคืขื•ืœื” ืขื ื’ื•ืจืžื™ ืฉื™ืขืชื•ืง ืื—ืจื™ื (ื›ืžื• p63, p73, NF-Y, SREBP, STAT3, ETS2, Sp1 ื•ืขื•ื“) ื•ืžืฉื ื” ืืช ื”ื‘ื™ื˜ื•ื™ ืฉืœ ื’ื ื™ื ืจื‘ื™ื.
  • ื”ืชื•ืฆืื•ืช:
    • ื”ื’ื‘ืจืช ื”ืชืจื‘ื•ืช ืชืื™ื โ€” ื”ืคืขืœืช ื’ื ื™ื ื›ืžื• cyclin A, B, CDK1 โ†’ ืžื—ื–ื•ืจ ืชื ืžื•ืืฅ.
    • ืงื™ื“ื•ื ื’ืจื•ืจื•ืช (metastasis) โ€” ืขื™ื“ื•ื“ EMT (epithelial-mesenchymal transition), ืฉื™ื ื•ื™ ื‘ืชื ื•ืขืช ื”ืชืื™ื, ืฉื™ืคื•ืจ ื ื“ื™ื“ื” ื•ื—ื“ื™ืจื” ืœืจืงืžื•ืช.
    • ื™ืฆื™ืจืช ื›ืœื™ ื“ื ื—ื“ืฉื™ื (angiogenesis) โ€” ื›ื“ื™ "ืœื”ื–ื™ืŸ" ืืช ื”ื’ื™ื“ื•ืœ.

ื‘ืฉื ื™ ื”ืžืงืจื™ื, ืฉื™ื ื•ื™ ื”ืงื™ืคื•ืœ (misfolding) ืžืฉื—ืง ืชืคืงื™ื“, ืื‘ืœ ื”ื”ืงืฉืจ ื”ืชืื™ ืงื•ื‘ืข ืื "ืฉื•ืžืจ ื”ื’ื ื•ื" ื”ื•ืคืš ืœ"ืฉื˜ืŸ" ืฉืžืงื“ื ืžื•ื•ืช ืชืื™ (ืืœืฆื”ื™ื™ืžืจ) ืื• ืฉืžืงื“ื ื”ืชืจื‘ื•ืช ืชืื™ (ืกืจื˜ืŸ).

ืžื–ื•ื ื•ืช ื•ืจื›ื™ื‘ื™ื ืฉืชื•ืžื›ื™ื ื‘ืคืขื™ืœื•ืช p53 ื”ืชืงื™ื ื”

ืžื—ืงืจื™ื ืชื•ืžื›ื™ื ื‘ืžื–ื•ืŸ ื›ืชืจื•ืคื”:

  • ื™ืจืงื•ืช ืžืžืฉืคื—ืช ื”ืžืฆืœื™ื‘ื™ื (ื‘ืจื•ืงื•ืœื™ ๐Ÿฅฆ , ื›ืจื•ื‘, ื›ืจื•ื‘ื™ืช, ืงื™ื™ืœ) โ€” ืขืฉื™ืจื™ื ื‘ืกื•ืœืคื•ืจืืคืŸ (Sulforaphane). ื–ื” ืžืคืขื™ืœ Nrf2 (ื ื•ื’ื“ ื—ืžืฆื•ืŸ), ืžืขื•ื“ื“ ืืคื•ืคื˜ื•ื–ื™ืก, ืขื•ืฆืจ ืžื—ื–ื•ืจ ืชื ื•ืžื’ืŸ ืขืœ ืชืื™ื ืžืคื ื™ ื ื–ืง. ื™ืฉ ืขื“ื•ื™ื•ืช ืœื”ืฉืคืขื” neuroprotective ื‘ืืœืฆื”ื™ื™ืžืจ (ื”ืคื—ืชืช ืืžื™ืœื•ืื™ื“ ื•ื˜ืื• ื‘ืžื•ื“ืœื™ื).
  • ืชื” ื™ืจื•ืง (EGCG) โ€” EGCG ื ืงืฉืจ ื™ืฉื™ืจื•ืช ืœืื–ื•ืจ N-terminal ืฉืœ p53, ืžืชื—ืจื” ืขื MDM2 (ื”ื—ืœื‘ื•ืŸ ืฉืžืคืจืง p53), ืžื’ืŸ ืขืœื™ื• ืžืคื ื™ ืคื™ืจื•ืง ื•ืžื’ื‘ื™ืจ ืจืžื•ืช ื•ืคืขื™ืœื•ืช p53. ื–ื” ืžืงื“ื ืืคืงื˜ ืื ื˜ื™-ืกืจื˜ื ื™.
  • ื›ื•ืจื›ื•ื (ื›ื•ืจื›ื•ืžื™ืŸ) โ€” ืžื™ื™ืฆื‘ p53, ืžืขื•ื“ื“ ืืคื•ืคื˜ื•ื–ื™ืก, ืžื“ื›ื ื“ืœืงืช ื•ืžืคืขื™ืœ ืžืกืœื•ืœื™ื ื›ืžื• miR-34 (ืชื•ืžืš ื‘ืคืขื™ืœื•ืช ื ื•ื’ื“ืช ื’ื™ื“ื•ืœ, ื’ื ื‘ืื•ืคืŸ ืขืฆืžืื™ ืž-p53 ื‘ื—ืœืง ืžื”ืžืงืจื™ื).
  • ืคื•ืœื™ืคื ื•ืœื™ื ื•ืคืœื‘ื ื•ืื™ื“ื™ื:
  • ืงื•ื•ืจืฆื˜ื™ืŸ (ื‘ืฆืœ ืกื’ื•ืœ, ืชืคื•ื—ื™ื, ืฆืœืคื™ื) โ€” ืžืขื•ื“ื“ ืืคื•ืคื˜ื•ื–ื™ืก ืชืœื•ื™-p53, ืขื•ืฆืจ ืžื—ื–ื•ืจ ืชื.
  • ืจื–ื‘ืจื˜ืจื•ืœ (ืขื ื‘ื™ื ืื“ื•ืžื™ื, ืคื™ืจื•ืช ื™ืขืจ) โ€” ืžื™ื™ืฆื‘ p53 ื•ืžื’ื‘ื™ืจ ืคืขื™ืœื•ืชื•.
  • ืืคื™ื’ื ื™ืŸ (ืคื˜ืจื•ื–ื™ืœื™ื”, ืกืœืจื™, ืคื™ืจื•ืช ื”ื“ืจ) โ€” ืžืกื™ื™ืข ืœืคืขื™ืœื•ืช p53 ื‘ื’ืจืขื™ืŸ ื•ืžืขื•ื“ื“ ืืคื•ืคื˜ื•ื–ื™ืก.
  • ืกืœื ื™ื•ื (ืื’ื•ื–ื™ ื‘ืจื–ื™ืœ, ื“ื’ื™ื, ืฉื•ื) โ€” ืžืฉืคืจ ืชื’ื•ื‘ืช p53 ืœื ื–ืง DNA, ืชื•ืžืš ื‘ืชื™ืงื•ืŸ ื•ืžื’ืŸ ืžืคื ื™ ืขืงื” ื—ืžืฆื•ื ื™ืช.
  • ืชื–ื•ื ื” ื“ืœืช ืกื•ื›ืจ/ืคื—ืžื™ืžื•ืช ืžืขื•ื‘ื“ื•ืช โ€” ืขื•ื–ืจืช ืœืฉืžื•ืจ ืขืœ ื™ืฆื™ื‘ื•ืช p53 ื•ืžืคื—ื™ืชื” ืœื™ืคื™ื“ื™ื ืžื–ื™ืงื™ื [ืžืงื•ืจ].
  • ืคื•ืœืื˜ – ื”ืฆื•ืจื” ื”ืคืขื™ืœื” ื‘ืœื‘ื“ ื ื—ืฉืฃ ื›ื•ื™ื˜ืžื™ืŸ ื—ื™ื•ื ื™ ืœืชื”ืœื™ื›ื™ื ืชืื™ื™ื ืงืจื™ื˜ื™ื™ื.  ื ื™ืกื•ื™ื™ื ื‘ื—ื™ื•ืช ื•ื‘ื‘ื ื™ ืื“ื ื”ืจืื• ืฉืžืชืŸ ืชื•ืกืคื™ ืคื•ืœืื˜ ื™ื›ื•ืœ ืœืฉืงื ืืช ืชืงื™ื ื•ืช ื”ื’ืŸ p53 ื•ืœืฆืžืฆื ืืช ื›ืžื•ืช ื”ืฉื‘ืจื™ื ื‘-DNA, ื‘ืชื ืื™ ืฉื”ื˜ื™ืคื•ืœ ื ื™ืชืŸ ืœืคื ื™ ื”ื•ืคืขืช ื ื’ืขื™ื ื˜ืจื•ื-ืกืจื˜ื ื™ื™ื [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3]. ืฆืจื™ื›ื” ื ืื•ืชื” ืฉืœ ืคื•ืœืื˜ (ื•ื•ื™ื˜ืžื™ืŸ B6) ื”ืคื—ื™ืชื” ืืช ื”ืกื™ื›ื•ืŸ ืœืกืจื˜ืŸ ืžืขื™ ื’ืก ื”ื›ื•ืœืœ ืžื•ื˜ืฆื™ื™ืช p53 ื‘ืฉื™ืขื•ืจ ืฉืœ ื›-40% ืขื“ 50% ื‘ื”ืฉื•ื•ืื” ืœืืœื• ืขื ืฆืจื™ื›ื” ื ืžื•ื›ื”. ืœื”ืฉืชืžืฉ ืจืง ื‘ืฆื•ืจื” ื”ืคืขื™ืœื” ืฉื‘ื” L-methylfolate. ืฆื•ืจื” ื–ื• ื—ื™ื•ื ื™ืช ื‘ืžื™ื•ื—ื“ ืœื”ื’ื ื” ืขืœ ื’ืŸ ื”-p53 ื•ืžื ื™ืขืช ืฉื‘ืจื™ื ื‘-DNA [ืžืงื•ืจ].

ื•ื™ื˜ืžื™ืŸ D3 (ืžื—ืฉื™ืคื” ืœืฉืžืฉ ืœืขื•ืœื ืœื ืžืชื•ืกืฃ, ื”ื’ื ืฉื” Ai ื™ืžืœื™ืฅ ืœืš ืขืœื™ื•, ื”ื•ื ืคื•ื’ืข ื‘ื’ืœื•ื˜ืชื™ื•ืŸ, ื•ื‘ืœื™ ื’ืœื•ื˜ืชื™ื•ืŸ ืื™ืŸ ื”ื—ืœืžื”) โ€” ืชื•ืžืš ื‘ืžืขืจื›ืช ื”ื—ื™ืกื•ืŸ ื•ื‘ื•ื•ื™ืกื•ืช ืชืื™, ื•ืขืฉื•ื™ ืœืชืžื•ืš ื‘ืขืงื™ืคื™ืŸ ื‘-p53 ื“ืจืš ื”ืคื—ืชืช ื“ืœืงืช [ืžืงื•ืจ].

ืงืืžื™ื ื• ืกืื ื˜ื™ืื’ื• ื“ื”ืงื•ืžืคื•ืกื˜ืœื”. ืžืกืœื•ืœ ื”ืœื™ื›ื”, ื ื’ื™ืฉ ื‘ืŸ 840 ืง"ืž ื‘ืฆืคื•ืŸ ืกืคืจื“. ื™ืจื•ืŸ ืžืจื’ื•ืœื™ืŸ ืฆื•ืขื“ ืœืœื™ืื•ืŸ 24.3.2017.

ืจื™ืงื•ื“๐Ÿคผโ€โ™€๏ธ, ืฉื—ื™ื”๐ŸŠโ›น๏ธ, ื•ื”ืœื™ื›ื” ๐Ÿšถื›ืชืจื•ืคื”

ืคืขื™ืœื•ืช ื’ื•ืคื ื™ืช ืžื—ืงืจื™ื ืžืชืงื“ืžื™ื ืฉื‘ื™ื ื•ืžืฆื‘ื™ืขื™ื ืขืœ ื›ืš ืฉืจืžื•ืช ื’ื‘ื•ื”ื•ืช ืฉืœ ืคืขื™ืœื•ืช ื’ื•ืคื ื™ืช, ื‘ื›ืœืœ ื–ื” ื˜ื™ืคื•ืœ ื‘ื’ื™ื ื”, ื ื™ืงื™ื•ืŸ ื”ื‘ื™ืช, ื•ื”ืœื™ื›ื” ืœืงื ื™ื•ืช ืขืฉื•ื™ื•ืช ืœื”ืคื—ื™ืช ืกืคืฆื™ืคื™ืช ืืช ื”ืกื™ื›ื•ืŸ ืœืžื•ื˜ืฆื™ื•ืช p53 ื‘ื’ื™ื“ื•ืœื™ื ื”ืจืกื ื™ื™ื (ืœืžืฉืœ ื‘ืจืงื˜ื•ื), ื ื•ืฉื ืฉืžื—ื–ืง ืืช ื”ื˜ืขื ื” ืฉืื•ืจื— ื—ื™ื™ื ืžืฉืคื™ืข ืขืœ ื”ืžืกืœื•ืœ ื”ืžื•ืœืงื•ืœืจื™ ืฉืœ ื”ืžื—ืœื” ืžืขืฆื™ื ื’ื•ืจื PGC-1ฮฑ,ื•ืžืงื“ื ืžืกืœื•ืœื™ ื ื™ืงื•ื™ ื•ื”ื—ืœืžื” [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3, ืžืงื•ืจ4]. ืฆืื• ืœืžืกืขื•ืช ื”ืœื™ื›ื”, ืื ื™ ื‘ืื•ืคืŸ ืื™ืฉื™ ืžืžืœื™ืฅ ืขืœ ืžืกืœื•ืœ ื”ื ืœื™ื›ื” ื‘ืฆืคื•ืŸ ืกืคืจื“ "ืงืืžื™ื ื• ืกื ื˜ื™ืื’ื• ื“ื” ืงื•ืžืคื•ืกื˜ืœื”" – ื›ืืŸ, ืจืžื•ืช ื’ื‘ื•ื”ื•ืช ืฉืœ ืคืขื™ืœื•ืช ื’ื•ืคื ื™ืช ืขืฉื•ื™ื•ืช ืœื”ืคื—ื™ืช ืกืคืฆื™ืคื™ืช ืืช ื”ืกื™ื›ื•ืŸ ืœืžื•ื˜ืฆื™ื•ืช ืฉืœ ื—ืœื‘ื•ืŸ – p53 ื‘ื’ื™ื“ื•ืœื™ ืกืจื˜ืŸ [ืžืงื•ืจ1, ืžืงื•ืจ2].

PGC-1ฮฑ ื›ืชืจื•ืคื”

ืคืขื™ืœื•ืช ื’ื•ืคื ื™ืช, ืžืงื“ืžืช ืกื™ื ื˜ื–ื” ืขืฆืžืื™ืช ืฉืœ PGC-1ฮฑ. ื‘ืžื™ื•ื—ื“ ืื™ืžื•ื ื™ ืกื‘ื•ืœืช, ืžื’ื‘ื™ืจื” ืืช ื”ื‘ื™ื˜ื•ื™ ืฉืœ PGC-1ฮฑ – (ืงื•-ืืงื˜ื™ื‘ื˜ื•ืจ-1 ืืœืคื ืฉืœ ืงื•ืœื˜ืŸ ื’ืžื ื”ืžื•ืคืขืœ ืขืœ ื™ื“ื™ ืคืจื•ืœื™ืกืจืื˜ื•ืจ ืคืจื•ืงืกื™ืกื•ื) ื‘ืฉืจื™ืจื™ ื”ืฉืœื“. PGC-1ฮฑ ืคื•ืขืœ ื›ื’ื•ืจื ืžืคืชื— ื‘ื‘ื™ื•ื’ื ื–ื” ืžื™ื˜ื•ื›ื•ื ื“ืจื™ืืœื™ืช (ื™ืฆื™ืจืช ืžื™ื˜ื•ื›ื•ื ื“ืจื™ื” ื—ื“ืฉื”, ืžื” ืฉืžืฉืคืจ ืืช ืžื ื•ืข ื”ื”ื—ืœืžื” ืฉืœ ื”ืชื) ื•ื—ื™ืœื•ืฃ ื—ื•ืžืจื™ื, ืชื•ืš ืฉื™ืชื•ืฃ ืคืขื•ืœื” ืขื ื”ื—ืœื‘ื•ืŸ P53 ๐Ÿฆโ€๐Ÿ”ฅ ืœืฉื™ืคื•ืจ ื”ืชืคืงื•ื“ ื”ืžื™ื˜ื•ื›ื•ื ื“ืจื™ืืœื™, ืžื ื™ืขืช ืกื˜ืจืก ื—ืžืฆื•ื ื™ ื•ืฉื™ืคื•ืจ ื”ื™ื›ื•ืœืช ื”ืื™ืจื•ื‘ื™ืช ื”ื›ืœืœื™ืช [ืžืงื•ืจ1, ืžืงื•ืจ2, ืžืงื•ืจ3, ืžืงื•ืจ4].

ื’ื•ืจืžื™ื ืžื–ื™ืงื™ื ื ื•ืกืคื™ื ืฉื™ืฉ ืœื”ื™ื–ื”ืจ ืžื”ื ื›ื•ืœืœ ื”ืžืœืฆื•ืช ืžื•ืžื—ื™ื ืฉืื™ื ื ืžืชืขื“ื›ื ื™ื ื‘ืžื—ืงืจ ื—ื“ืฉ

  • ืขื™ืฉื•ืŸ, ื–ื™ื”ื•ื ืื•ื•ื™ืจโ€” ื—ื•ืžืจื™ื ืžืกืจื˜ื ื™ื (ื“ื™ืื•ืงืกื™ืŸ, TMAO, ืฉืžืงื•ืจื• ื‘ื‘ืฉืจ) ื’ื•ืจืžื™ื ืœืžื•ื˜ืฆื™ื•ืช ื™ืฉื™ืจื•ืช ื‘ื’ืŸ TP53 [ืžืงื•ืจ].
  • ืงืจื™ื ื” (UV, ืจื ื˜ื’ืŸ) โ€” ืžืคืขื™ืœื” p53 ืื‘ืœ ืขืœื•ืœื” "ืœืฉื—ื•ืง" ืื•ืชื• ื–ื• ื’ื ื”ืกื™ื‘ื” ืœืžื™ื ื•ืŸ ืžื“ื•ื™ืง ืฉืœ ื–ืžืŸ ื”ื—ืฉื™ืคื” ืœืฉืžืฉ๐ŸŒž.
  • ืจืขืœื™ื (ืžืชื›ื•ืช ื›ื‘ื“ื•ืช, ื—ื•ืžืจื™ ื”ื“ื‘ืจื”) โ€” ืžืฉื‘ืฉื™ื p53, ืœื›ืŸ ื”ื”ืžืœืฆื” ืขืœ ื™ืจืงื•ืช ืื•ืจื’ื ื™ื™ื, ืœื‘ื“ื•ืง ืืช ืžืงื•ืจ ื”ืืฆื•ืช ื•ื”ื“ื’ื™ื.

ื˜ื™ืคื•ืœื™ื ื•ืชืจื•ืคื•ืช

  • ืกื˜ื˜ื™ื ื™ื (ืœื”ื•ืจื“ืช ื›ื•ืœืกื˜ืจื•ืœ) โ€” ื‘ืžืคืชื™ืข, ื”ื ื™ื›ื•ืœื™ื ืœืงื“ื ืคื™ืจื•ืง ืฉืœ p53 ืžื•ื˜ื ื˜ื™ (ื‘ืžื™ื•ื—ื“ conformational mutants) ื“ืจืš ืขื™ื›ื•ื‘ ื ืชื™ื‘ ื”ืžื•ื•ืœื•ื ื˜, ื•ืœื”ืคื—ื™ืช GOF. ื–ื” ื ื—ืงืจ ื›ื˜ื™ืคื•ืœ ืžืฉืœื™ื ื‘ืกืจื˜ืŸ ืขื ืžื•ื˜ืฆื™ื•ืช p53. ื–ืืช ื‘ืฉืขื” ืฉ 4 ื›ืคื•ืช ืฉื™ื‘ื•ืœืช ืฉื•ืขืœ ื‘ื›ืœ ื‘ืงืจ ื™ื›ื•ืœื•ืช ืœื”ื‘ื™ื ืœืชื•ืฆืื” ืžื•ืคืœืื” – ืขื•ื“ ืขืœ ื›ืš ื›ืืŸ
  • ื›ื™ืžื•ืชืจืคื™ื”/ืงืจื™ื ื” โ€” ืžืคืขื™ืœื™ื p53 ื‘ืชืื™ื ืกืจื˜ื ื™ื™ื, ืื‘ืœ ืคื•ื’ืขื™ื ื’ื ื‘ืชืื™ื ื‘ืจื™ืื™ื.
  • ืžืขื›ื‘ื™ ืคืจื•ื˜ืื–ื•ื โ€” ืžืฉืคื™ืขื™ื ืขืœ ืคื™ืจื•ืง ื—ืœื‘ื•ื ื™ื, ื›ื•ืœืœ p53.

MDM2 โ€” ื—ืœื‘ื•ืŸ ืฉืžืคืจืง p53 ื‘ืื•ืคืŸ ืžื‘ื•ืงืจ ื‘ืชืื™ื ื‘ืจื™ืื™ื. ืฉื™ื‘ื•ืฉื™ื ื‘ื• ืžืฉื ื™ื ืจืžื•ืช p53.

ืœืกื™ื›ื•ื โ€“ ื’ื™ืฉื” ืชื–ื•ื ืชื™ืช ืชื•ืžื›ืช

ืชื–ื•ื ื” ืขืฉื™ืจื” ื‘ื™ืจืงื•ืช ืžืฆืœื™ื‘ื™ื, ืชื” ื™ืจื•ืง, ื›ื•ืจื›ื•ื, ืคื™ืจื•ืช ื™ืขืจ/ืชืคื•ื—ื™ื, ื‘ืฆืœ ืกื’ื•ืœ, ื“ื’ื™ื, ืื’ื•ื–ื™ื (ืกืœื ื™ื•ื), ืขื ื”ื’ื‘ืœื” ืฉืœ ืฉื•ืžืŸ ืจื•ื•ื™, ืฉื•ืžืŸ ื˜ืจืื ืก, ื‘ืฉืจ ืื“ื•ื ืžืขื•ื‘ื“, ืกื•ื›ืจื™ื ื•ืžื–ื•ืŸ ืžืขื•ื‘ื“ โ€“ ื™ื›ื•ืœื” ืœืชืžื•ืš ื‘-p53 ื”ืชืงื™ืŸ, ืœื”ืคื—ื™ืช ืขืงื” ื—ืžืฆื•ื ื™ืช, ืœื™ื™ืฆื‘ ืืช ื”ื—ืœื‘ื•ืŸ ื•ืœื“ื›ื ืชื”ืœื™ื›ื™ื ื“ืœืงืชื™ื™ื/ืžืกืจื˜ื ื™ื [ืžืงื•ืจ]. ื”ืจื•ืคื ืฉืœืš ื™ื’ื™ื“ ื–ื” ืœื "ืชืจื•ืคื”" [ืžืงื•ืจ], ืื‘ืœ ืขื“ื•ื™ื•ืช ื—ื–ืงื•ืช ืžืฆื‘ื™ืขื•ืช ืขืœ ืืคืงื˜ ืžื’ืŸ ื•ืžืฉืคืจ (ื‘ืžื™ื•ื—ื“ ื‘ืžื ื™ืขื” ื•ื‘ืชืžื™ื›ื” ื‘ื˜ื™ืคื•ืœื™ื).

ื”ืžืœืฆื” ื—ืฉื•ื‘ื”: ื–ื” ืœื ืชื—ืœื™ืฃ ืœื™ื™ืขื•ืฅ ืจืคื•ืื™. ืื ื™ืฉ ื—ืฉื“ ืœืกืจื˜ืŸ, ืืœืฆื”ื™ื™ืžืจ ืื• ื‘ืขื™ื•ืช ืžื˜ื‘ื•ืœื™ื•ืช โ€“ ืคื ื” ืœืจื•ืคื/ืื•ื ืงื•ืœื•ื’/ื ื•ื™ืจื•ืœื•ื’. ืชื•ืกืคื™ื (ื›ืžื• ื›ื•ืจื›ื•ืžื™ืŸ, EGCG) ืขืœื•ืœื™ื ืœื”ืฉืคื™ืข ืขืœ ืชืจื•ืคื•ืช, ื•ืกื˜ื˜ื™ื ื™ื ื“ื•ืจืฉื™ื ืžืขืงื‘.

ืœื‘ืกื•ืฃ

ื‘ืกื‘ื™ื‘ื” ืžื›ื‘ื“ืช ื—ืœื‘ื•ืŸ ื”-p53 "ืฉื•ืžืจ ื”ื’ื ื•ื" ื‘ืชืคืงื™ื“ื• ื›ื ื•ื’ื“ ืกืจื˜ืŸ ืžื•ื ืข ืžืชืื™ื ืคื’ื•ืžื™ื ืœื”ืฉืชื›ืคืœ. ืขื ื–ืืช, ื‘ืžื—ืœืช ืืœืฆื”ื™ื™ืžืจ ืœืžืฉืœ ื ืžืฆื ืฉืžืชืจื—ืฉื™ื ื‘ื• ืฉื™ื ื•ื™ื™ื ืงืจื™ื˜ื™ื™ื ืฉื”ื•ืคื›ื™ื ืื•ืชื• ืœืจืฉืขื•ืช ื ื˜ื•.



ืกื™ื›ื•ื ืคืฉื•ื˜ โ€“ ื—ืœืง ื“'

ื”ืจืขื™ื•ืŸ ื”ืžืจื›ื–ื™:

p53 ื”ื•ื ืื—ื“ ืžื—ืœื‘ื•ื ื™ ื”ื”ื’ื ื” ื”ื—ืฉื•ื‘ื™ื ื‘ื™ื•ืชืจ ื‘ื’ื•ืฃ โ€“ ืžื›ื•ื ื” "ืฉื•ืžืจ ื”ื’ื ื•ื".
ื”ื•ื ืคื•ืขืœ ื›ืžื• "ืฉื•ื˜ืจ" ืื• "ืžื ื”ืœ ืื™ื›ื•ืช" ื‘ืชื:

  • ืžื–ื”ื” ื ื–ืง ืœ-DNA
  • ืขื•ืฆืจ ืืช ื—ืœื•ืงืช ื”ืชื ื›ื“ื™ ืœืชืงืŸ ืืช ื”ื ื–ืง
  • ืื ื”ื ื–ืง ื—ืžื•ืจ ืžื“ื™ โ€“ ืžืคืขื™ืœ ืืคื•ืคื˜ื•ื–ื™ืก (ืžื•ื•ืช ืชืื™ ืžืชื•ื›ื ืŸ) ื›ื“ื™ ืœืžื ื•ืข ืกืจื˜ืŸ

ื›ืฉื”-p53 ืขื•ื‘ื“ ื˜ื•ื‘ โ€“ ื”ืชืื™ื ื ืฉืืจื™ื ื‘ืจื™ืื™ื ื•ื”ื’ื•ืฃ ืžืฆืœื™ื— ืœืžื ื•ืข ื”ืชืคืชื—ื•ืช ื’ื™ื“ื•ืœื™ื ื•ืœื”ืื˜ ื”ื–ื“ืงื ื•ืช.
ื›ืฉื”-p53 ื ื—ืœืฉ (ืขืงื‘ ืขื•ื“ืฃ ืฉืคืข, ื“ืœืงืช ื›ืจื•ื ื™ืช, ืกื˜ืจืก ื—ืžืฆื•ื ื™) โ€“ ื”ืกื™ื›ื•ืŸ ืœืกืจื˜ืŸ ืขื•ืœื” ืžืฉืžืขื•ืชื™ืช (ื”ื•ื ืคื’ื•ื ื‘ื™ื•ืชืจ ืž-50% ืžืกื•ื’ื™ ื”ืกืจื˜ืŸ).

ื”ืงืฉืจ ืœืฆื™ืจื™ื ื”ืื—ืจื™ื:
ืฉืคืข ื›ืจื•ื ื™ (ืขื•ื“ืฃ mTOR) ืžื“ื›ื ืืช p53, ื‘ืขื•ื“ ื”ืคืขืœืช AMPK (ื“ืจืš ืฆื•ื, ืคืขื™ืœื•ืช ื’ื•ืคื ื™ืช ื•ื”ื’ื‘ืœื” ืžื‘ื•ืงืจืช) ืžื—ื–ืงืช ืื•ืชื•.

ื”ืžืกืจ ื”ืžืขืฉื™:

ื›ื“ื™ ืœืฉืžื•ืจ ืขืœ p53 ื—ื–ืง ืฆืจื™ืš:

  • ืœื”ืคื—ื™ืช ืขื•ืžืก ืžื˜ื‘ื•ืœื™ ื•ื“ืœืงืช ื›ืจื•ื ื™ืช
  • ืœื”ืคืขื™ืœ ืžื—ื–ื•ืจื™ื•ืช ืฉืœ ืžื—ืกื•ืจ ืงืœ (ืฆื•ื, ืื™ืžื•ืŸ)
  • ืœืฆืจื•ืš ื—ื•ืžืจื™ื ื˜ื‘ืขื™ื™ื ืฉืชื•ืžื›ื™ื ื‘-p53 (ืกื•ืœืคื•ืจืคืืŸ๐Ÿฅฆ, ื›ื•ืจื›ื•ืžื™ืŸ, ืจืกื‘ืจื˜ืจื•ืœ๐Ÿ‡, ืงื•ื•ืจืฆื˜ื™ืŸ ๐Ÿง…ื•ืขื•ื“)

ื”ืขืจื” ื—ืฉื•ื‘ื”:
ืฉื™ื ื•ื™ ืชืคืจื™ื˜ ื”ืชื–ื•ื ื” ื•ื”ืคืกืงืช ื”ื”ืจืขืœื” ื”ืฉื•ื˜ืคืช ืฉืœ ื”ื’ื•ืฃ (ืกื•ื›ืจ, ืฉืžื ื™ื ืžื–ื•ืงืงื™ื, ืžื–ื•ืŸ ืžืขื•ื‘ื“, ื’ื‘ื™ื ื•ืช ืงืฉื•ืช, ื‘ืฉืจ ื•ื›ื•') ื”ื•ื ืื—ื“ ื”ืฆืขื“ื™ื ื”ืงืฉื™ื ื‘ื™ื•ืชืจ ืžื‘ื—ื™ื ื” ื ืคืฉื™ืช ื•ืจื’ืฉื™ืช. ื–ื” ื“ื•ืจืฉ ื”ืชืžื•ื“ื“ื•ืช ืขื ื”ืจื’ืœื™ื ืขืžื•ืงื™ื, ื”ืชืžื›ืจื•ื™ื•ืช ื•ืชื—ื•ืฉืช ื—ื•ืกืจ. ืืš ื–ื• ืœืขื™ืชื™ื ืงืจื•ื‘ื•ืช ื”ื ืงื•ื“ื” ืฉื‘ื” ืžืชื—ื™ืœื” ื”ื”ื—ืœืžื” ื”ืืžื™ืชื™ืช.

ื‘ืฉื•ืจื” ื”ืชื—ืชื•ื ื”:

p53 ื”ื•ื ื”ื“ื•ื’ืžื” ื”ืงืœืืกื™ืช ืœื›ืš ืฉื”ื’ื•ืฃ ืฉืœื ื• ืžืฆื•ื™ื“ ื‘ืžืขืจื›ื•ืช ื”ื’ื ื” ืžืชืงื“ืžื•ืช.
ื”ืชืคืงื™ื“ ืฉืœื ื• ื”ื•ื ืœื "ืœืชืช ืชืจื•ืคื”", ืืœื ืœืืคืฉืจ ืœืžืขืจื›ื•ืช ื”ืืœื” ืœืขื‘ื•ื“ ื›ืžื• ืฉืฆืจื™ืš โ€“ ืขืœ ื™ื“ื™ ื”ืกืจืช ืขื•ืžืกื™ื ื•ืฉืžื™ืจื” ืขืœ ืื•ืจื— ื—ื™ื™ื ืžื—ื–ื•ืจื™ ื•ืžืื•ื–ืŸ.


ืกื™ื›ื•ื ื›ืœืœื™ โ€“ ืืจื‘ืขืช ื—ืœืงื™ ื”ืกื“ืจื” (ื—ืœืงื™ื ื'-ื“')

ื”ืจืขื™ื•ืŸ ื”ืžืจื›ื–ื™ ืฉืœ ืกื“ืจืช ื”ืžืืžืจื™ื ืขืœ ืฆื™ืจื™ ื”ื”ื—ืœืžื”:

ื”ื’ื•ืฃ ืฉืœื ื• ืžืฆื•ื™ื“ ื‘ืžืขืจื›ื•ืช ื”ื—ืœืžื” ืขื•ืฆืžืชื™ื•ืช ื•ืžืชืงื“ืžื•ืช, ืื‘ืœ ื”ืŸ ื‘ื“ืจืš ื›ืœืœ ื—ืกื•ืžื•ืช ื‘ื’ืœืœ ืขื•ืžืก ืžืชืžืฉืš (ืฉืคืข ืงืœื•ืจื™, ื“ืœืงืช ื›ืจื•ื ื™ืช, ืžื–ื•ืŸ ืžื–ื™ืง, ืกื˜ืจืก).
ื”ื—ืœืžื” ืืžื™ืชื™ืช ืื™ื ื” "ื˜ื™ืคื•ืœ ื—ื“ื™ืฉ" ืื• ื›ื“ื•ืจ, ืืœื ืฉื™ื ื•ื™ ืชื ืื™ื ืฉืžืืคืฉืจ ืœื’ื•ืฃ ืœื”ืคืขื™ืœ ืืช ืžื ื’ื ื•ื ื™ ื”ืจื™ืคื•ื™ ื”ื˜ื‘ืขื™ื™ื ืฉืœื•.

ื”ืฆื™ืจื™ื ื”ืžืจื›ื–ื™ื™ื ืฉืžื•ืฆื’ื™ื ื‘ืกื“ืจื”:

  • AMPK โ€“ ืžืชื’ ื”ืื ืจื’ื™ื” ื•ื”ืื—ืจื™ื•ืช. ื ื“ืœืง ื‘ืžื—ืกื•ืจ ืงืœ ื•ืžืคืขื™ืœ ื ื™ืงื•ื™ ืชืื™ื (ืื•ื˜ื•ืคื’ื™ื”) ื•ืฉื™ืคื•ืจ ื”ืžื™ื˜ื•ื›ื•ื ื“ืจื™ื”.
  • mTOR โ€“ ืžืชื’ ื”ื‘ื ื™ื™ื”. ื—ื™ื•ื ื™ ื‘ืžื™ื“ื”, ืื‘ืœ ืฉืคืข ื›ืจื•ื ื™ ืžื“ื›ื ืืช ื”ื”ื—ืœืžื”.
  • PGC-1ฮฑ โ€“ ื‘ื ื™ื™ืช ืžืคืขืœื™ ืื ืจื’ื™ื” ื—ื“ืฉื™ื ื‘ืชืื™ื.
  • p53 โ€“ "ืฉื•ืžืจ ื”ื’ื ื•ื". ืžื–ื”ื” ื ื–ืง DNA, ืžืชืงืŸ ืื• ืžืฉืžื™ื“ ืชืื™ื ืคื’ื•ืžื™ื ื›ื“ื™ ืœืžื ื•ืข ืกืจื˜ืŸ. ืฉื•ืžืจ ื”ื’ื ื•ื", ื”ื•ื ืื—ื“ ืžื—ืœื‘ื•ื ื™ ื”ืจื™ืคื•ื™ ื”ื—ืฉื•ื‘ื™ื ื‘ื™ื•ืชืจ. ื”ื•ื ืžื–ื”ื” ื ื–ืง ืœ-DNA ๐Ÿงฌ, ืขื•ืฆืจ ื—ืœื•ืงื” ืคื’ื•ืžื” ื•ืžืคืขื™ืœ ืชื™ืงื•ืŸ ืื• ืืคื•ืคื˜ื•ื–ื™ืก.

ื—ืฉื•ื‘ ืœืฆื™ื™ืŸ:
p53 ื”ื•ื ื“ื•ื’ืžื” ืžืจื›ื–ื™ืช ื•ืžืฉืžืขื•ืชื™ืช ืœื—ืœื‘ื•ืŸ ืจื™ืคื•ื™, ืืš ื”ื•ื ืื™ื ื• ื—ืœื‘ื•ืŸ ื™ื—ื™ื“ ืžืกื•ื’ื•. ื”ื’ื•ืฃ ืžืคืขื™ืœ ื—ืœื‘ื•ื ื™ื ื•ืžื ื’ื ื•ื ื™ื ืจื‘ื™ื ื ื•ืกืคื™ื (ื›ื’ื•ืŸ Nrf2, SIRT1, FOXO, ATM ื•ืขื•ื“) ืฉืคื•ืขืœื™ื ื™ื—ื“ ื›ืจืฉืช ืžื•ืจื›ื‘ืช ืฉืœ ื”ื’ื ื”, ืชื™ืงื•ืŸ ื•ื”ืชื—ื“ืฉื•ืช.

ืืจื‘ืขืช ื”ืขืงืจื•ื ื•ืช ื”ื—ืฉื•ื‘ื™ื ื‘ืกื“ืจื”:

  1. ื”ืกืจื” ืœืคื ื™ ื”ื•ืกืคื” โ€“ ืงื•ื“ื ื›ืœ ืœื”ืคืกื™ืง ืœื”ืจืขื™ืœ ืืช ื”ื’ื•ืฃ ื•ืœื”ืคื—ื™ืช ืขื•ืžืกื™ื (ื”ืฆืขื“ ืฉื”ื›ื™ ืžืชืขืœืžื™ื ืžืžื ื•).
  2. ืžื—ื–ื•ืจื™ื•ืช โ€“ ื”ื’ื•ืฃ ื–ืงื•ืง ืœืฉืคืข + ืžื—ืกื•ืจ ืžื‘ื•ืงืจ (ืฆื•ื ืœืกื™ืจื•ื’ื™ืŸ, ืื™ืžื•ืŸ, ื”ืคื—ืชืช ื—ืœื‘ื•ืŸ/ืงืœื•ืจื™ื•ืช).
  3. ื”ื•ืจืžื–ื™ืก โ€“ ืกื˜ืจืก ืงืœ ื•ืžื‘ื•ืงืจ ืžื—ื–ืง ืืช ื”ื’ื•ืฃ (ืชื ื•ืขื”, ืฆื•ื, ืฆืžื—ื™ื ืขืฉื™ืจื™ื ื‘ืกื•ืœืคื•ืจืคืืŸ, ืจืกื‘ืจื˜ืจื•ืœ ื•ื›ื•').
  4. ืคืขื ื•ื— โ€“ ืืคืฉืจ ืœืจืื•ืช ืฉื™ืคื•ืจ ื“ืจืš "ื˜ื‘ื™ืขื•ืช ืืฆื‘ืข" ื‘ื‘ื“ื™ืงื•ืช ื“ื ืจื’ื™ืœื•ืช (ื˜ืจื™ื’ืœื™ืฆืจื™ื“ื™ื โ†“, TG/HDL โ†‘, CRP โ†“, ืฉื™ืคื•ืจ eGFR ื•ื›ื•').

ื”ืžืกืจ ื”ื—ืฉื•ื‘ ื‘ื™ื•ืชืจ:

ื”ื’ื•ืฃ ื™ื•ื“ืข ืœื”ื—ืœื™ื ื”ืจื‘ื” ื™ื•ืชืจ ื˜ื•ื‘ ืžืžื” ืฉืื ื—ื ื• ื—ื•ืฉื‘ื™ื โ€“ ื‘ืชื ืื™ื ื”ื ื›ื•ื ื™ื.
ื”ืืชื’ืจ ื”ื’ื“ื•ืœ ื”ื•ื ืœื ืจืง ื”ื™ื“ืข, ืืœื ื’ื ื”ืงื•ืฉื™ ื”ื ืคืฉื™ ื‘ืฉื™ื ื•ื™ ื”ืจื’ืœื™ื, ื‘ื”ืคืกืงืช ืžื–ื•ืŸ ืžืจื’ื™ืข/ืžืžื›ืจ ื•ื‘ื”ืชืžื•ื“ื“ื•ืช ืขื ืชื—ื•ืฉืช ื—ื•ืกืจ.

ื‘ืฉื•ืจื” ื”ืชื—ืชื•ื ื”:

ื”ื—ืœืžื” ื”ื™ื ืœื ืžืœื—ืžื” ื ื’ื“ ื”ื’ื•ืฃ, ืืœื ืฉื™ืชื•ืฃ ืคืขื•ืœื” ืื™ืชื•.
ื›ืฉืžืคืกื™ืงื™ื ืืช ื”ื ื–ืง ื•ืžืคืขื™ืœื™ื ืืช ื”ืฆื™ืจื™ื ื”ื ื›ื•ื ื™ื (AMPK, p53 ื•ื›ื•'), ื”ื’ื•ืฃ ื™ื›ื•ืœ ืœื‘ืฆืข ืชื™ืงื•ื ื™ื ืขืžื•ืงื™ื โ€“ ื’ื ื‘ืžืฆื‘ื™ื ืฉื ื—ืฉื‘ื™ื "ื›ืจื•ื ื™ื™ื".

ื—ืœืงย ื”'ย โ€“ ื—ืœื‘ื•ื ื™ ื”ื”ื—ืœืžื”: ื”ืจืฉืช ื”ืžื•ืœืงื•ืœืจื™ืช ืฉืœ ื”ืจื™ืคื•ื™, ื”ื”ืชื—ื“ืฉื•ืช ื•ื”ื”ื•ืžืื•ืกื˜ื–ื™ืก ืžืืช ื™ืจื•ืŸ ืžืจื’ื•ืœื™ืŸ


ื™ืจื•ืŸ ืžืจื’ื•ืœื™ืŸ

ื ืฉืืจื• ืœืš ืฉืืœื•ืช

๐Ÿ”ฌืืฉืžื— ืœื”ืฉื™ื‘ ืขืœ ื›ืœ ืฉืืœื”

ื‘ื‘ืงืฉื” ืœื ืœื”ืชืงืฉืจ ืžืฉื•ื ืฉื–ื” ืคืฉื•ื˜ ืœื ืžืืคืฉืจ ืœื™ ืœืขื‘ื•ื“ โ€“ ืื ื ื”ืฉืชืžืฉื• ื‘ืืžืฆืขื™ื ืฉืœืคื ื™ื›ื

    ืฉืžื™ Name:


    ื˜ืœืคื•ืŸ phone:


    ื“ื•ื"ืœ (ื›ื“ื™ ืฉืื•ื›ืœ ืœื”ืฉื™ื‘ ืœืš ืžื›ืœ ืžืงื•ื ื‘ืขื•ืœื) Email:


    ืื™ืš ืื ื™ ื™ื›ื•ืœ ืœืขื–ื•ืจ ืœืš How can I help you:


    ืืคืฉืจ ืœืงื‘ืœ ืืช ื‘ื“ื™ืงื•ืช ื”ื“ื ื”ื—ืจื™ื’ื•ืช ืฉืœืš Exceptional laboratory tests:


    ืœืžืขืŸ ื”ืกืจ ืกืคืงื—ื•ื‘ืช ื”ืชื™ื™ืขืฆื•ืช ืขื ืจื•ืคื (ื”ืžื›ื™ืจ ืœืคืจื˜ื™ื ืืช ืžืฆื‘ื• ื”ื‘ืจื™ืื•ืชื™ ื”ื›ืœืœื™ ืฉืœ ื›ืœ ืžื˜ื•ืคืœ ืื• ืฉืœืš) ืœืคื ื™ ืฉื™ืžื•ืฉ ื‘ื›ืœ ืชื›ืฉื™ืจ, ืžืื›ืœ, ืชืžืฆื™ืช ืื• ื‘ื™ืฆื•ืข ื›ืœ ืชืจื’ื™ืœ. ื™ืจื•ืŸ ืžืจื’ื•ืœื™ืŸ ื”ื•ื ืจืงื“ืŸ ื•ืžื‘ื™ืช ื”ืžื—ื•ืœ ืฉืœื• ื‘ื™ืจื•ืฉืœื™ื ืคืจืฆื” ื”ืชื•ืจื” ื›ืืฉืจ ื ื—ืฉืคื” ืฉื™ื˜ืช ื”ืžื—ื•ืœ ืฉืœื• ื›ื‘ืขืœืช ื™ื›ื•ืœืช ืžื“ื”ื™ืžื”, ื‘ืืžืฆืข ืฉื ื•ืช ื” โ€“ 80 ืœืจืคื ืกืจื˜ืŸ. ื”ืžื™ื“ืข ื‘ืืชืจ ืฉืœ ื™ืจื•ืŸ ืžืจื’ื•ืœื™ืŸ ืื• ื‘ืืชืจ "ืœื—ื™ืฆื•ืช ื”ื”ื—ืœืžื”" (ื‘ืคื™ืกื‘ื•ืง ืื• MARGOLINMETHOD.COM ), ื‘ืžืืžืจ ื”ื "ืœ ื•ื‘ืžืืžืจื™ื ืฉืœ ื™ืจื•ืŸ ืžืจื’ื•ืœื™ืŸ ื”ื ื—ื•ืžืจ ืœืžื—ืฉื‘ื” โ€“ ืคื™ืœื•ืกื•ืคื™ื” ืœื ื”ืžืœืฆื” ื•ืœื ื”ื ื—ื™ื™ื” ืœืฆื™ื‘ื•ืจ ืœื”ืฉืชืžืฉ ืื• ืœื—ื“ื•ืœ ืžืœื”ืฉืชืžืฉ ื‘ืชืจื•ืคื•ืช โ€“ ืื™ืŸ ื‘ืžื™ื“ืข ื‘ืืชืจ ื–ื” ืื• ื‘ื›ืœ ืื—ื“ ืžื”ืžืืžืจื™ื ืชื—ืœื™ืฃ ืœื”ื™ื•ื•ืขืฆื•ืช ืขื ืžื•ืžื—ื” ืžื•ื›ืจ ื”ืžื›ื™ืจ ืœืคืจื˜ื™ื ืืช ืžืฆื‘ื• ื”ื‘ืจื™ืื•ืชื™ ื”ื›ืœืœื™ ืฉืœืš ื•ืฉืœ ืžืฉืคื—ืชืš. ืžื•ืžืœืฅ ืชืžื™ื“ ืœื”ืชื™ื™ืขืฅ ืขื ืจื•ืคื ืžื•ืกืžืš ืื• ืจื•ืงื— ื‘ื›ืœ ื”ื ื•ื’ืข ื‘ื›ืื‘, ื”ืจื’ืฉื” ืจืขื” ืื• ืœืžื˜ืจื•ืช ื•ืื•ืคืŸ ื”ืฉื™ืžื•ืฉ, ื‘ืžื–ื•ื ื•ืช, ืžืฉื—ื•ืช, ืชืžืฆื™ื•ืช ื•ืืคื™ืœื• ื‘ืชืจื’ื™ืœื™ื, ืื• ื‘ืชื›ืฉื™ืจื™ื ืื—ืจื™ื ืฉื ื–ื›ืจื™ื ื›ืืŸ.

     physician (who knows in detail the general health of each patient or yours) before using any medicine, food, extract or any exercise. The information on Yaron Margolin's website or the "Healing Presses" website (on Facebook or YARONMARGOLIN.COM), in the above article and in Yaron Margolin's articles are material for thought โ€“ philosophy neither recommendation nor public guidance to use or cease to use drugs โ€“ no information on this site or anyone You should always consult with a qualified physician or pharmacist regarding pain, bad feeling, or goals and how to use foods, ointments, extracts and even exercises, or other remedies that are mentioned as such

    ืžืืžืจื™ื ืื—ืจื•ื ื™ื

    ื ืฉืœื— ื‘ ื›ืœืœื™

    ื›ืชื™ื‘ืช ืชื’ื•ื‘ื”

    Or

    ื”ืื™ืžื™ื™ืœ ืœื ื™ื•ืฆื’ ื‘ืืชืจ. ืฉื“ื•ืช ื”ื—ื•ื‘ื” ืžืกื•ืžื ื™ื *

    *