ALKBH3 m1A Demethylase Deficiency Reduces Alzheimer's Amyloid-β Pathology - PubMed
a day ago
- #Alzheimer's disease
- #mitophagy
- #RNA modifications
- ALKBH3 m1A demethylase deficiency reduces Alzheimer's amyloid-β pathology.
- N1-methyladenosine (m1A) is the most altered RNA modification in 5xFAD mice, an Aβ AD model.
- ALKBH3, a demethylase regulator of m1A, is upregulated in Alzheimer's disease (AD).
- Reduction of Alkbh3 decreases Aβ plaques and restores cognition in AD models.
- Elevated ALKBH3 levels impair neuronal morphology and mitochondrial function by disrupting mitophagy.
- ALKBH3 removes m1A from PINK1 mRNA, a key regulator of mitophagy.
- ALKBH3 is elevated in human AD and is linked to mitophagy impairment.
- Depletion of ALKBH3 confers neuroprotection, presenting it as a therapeutic target in AD.