A variant of the autophagic receptor NDP52 counteracts phospho-TAU accumulation and emerges as a protective factor for Alzheimer's disease.

ABSTRACT: Selective elimination of early pathological TAU species may be a promising therapeutic strategy to reduce the accumulation of TAU, which contributes to neurodegeneration and is a hallmark of Alzheimer's disease (AD). Pathological hyper-phosphorylated TAU can be degraded through selective autophagy, and NDP52/CALCOCO2 is one of the autophagy receptors involved in this process. In 2021, we discovered a variant of NDP52, called NDP52^GE (rs550510), that is more efficient at promoting autophagy. We here anticipate that this variant could be a powerful factor that could eliminate pathological forms of TAU better than its WT form (NDP52^WT). Indeed, we provide evidence that in in vitro systems and in a Drosophila melanogaster model of TAU-induced AD, the NDP52^GE va

SUBMITTER: Mattioni A 

PROVIDER: S-EPMC12000434 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature