Calcineurin-mediated regulation of growth-associated protein 43 is essential for neurite and synapse formation and protects against α-synuclein-induced degeneration.

ABSTRACT:

Introduction

Elevated calcium (Ca²⁺) levels and hyperactivation of the Ca²⁺-dependent phosphatase calcineurin are key factors in α-synuclein (α-syn) pathobiology in Dementia with Lewy Bodies and Parkinson's Disease (PD). Calcineurin activity can be inhibited by FK506, an FDA-approved compound. Our previous work demonstrated that sub-saturating doses of FK506 provide neuroprotection against α-syn pathology in a rat model of α-syn neurodegeneration, an effect associated with the phosphorylation of growth-associated protein 43 (GAP-43).

Methods

To investigate the role of GAP-43 phosphorylation, we generated phosphomutants at the calcineurin-sensitive sites and expressed them in PC12 cells and primary rat cortical neuronal cultures to assess their effects o

SUBMITTER: Grebenik E 

PROVIDER: S-EPMC12009912 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature