Microtubule-affinity regulating kinase family members distinctively affect tau phosphorylation and promote its toxicity in a Drosophila model.

ABSTRACT: Accumulation of abnormally phosphorylated tau and its aggregation constitute a significant hallmark of Alzheimer's disease (AD). Tau phosphorylation at Ser262 and Ser356 in the KXGS motifs of microtubule-binding repeats plays a critical role in its physiological function and AD disease progression. Major tau kinases to phosphorylate tau at Ser262 and Ser356 belong to the Microtubule Affinity Regulating Kinase family (MARK1-4), which are considered one of the major contributors to tau abnormalities in AD. However, whether and how each member affects tau toxicity in vivo is unclear. We used transgenic Drosophila as a model to compare the effect on tau-induced neurodegeneration among MARKs in vivo. MARK4 specifically promotes tau accumulation and Ser396 phosphorylation, which yields more tau

SUBMITTER: Sultanakhmetov G 

PROVIDER: S-EPMC11447834 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature