Manganese exposure induces parkinsonism-like symptoms by Serpina3n-TFEB-v/p-ATPase signaling mediated lysosomal dysfunction.

ABSTRACT: Manganese (Mn) is a neurotoxin that has been etiologically linked to the development of neurodegenerative diseases in the case of overexposure. It is widely accepted that overexposure to Mn leads to manganism, which has clinical symptoms similar to Parkinson's disease (PD), and is referred to as parkinsonism. Astrocytes have been reported to scavenge and degrade extracellular α-synuclein (α-Syn) in the brain. However, the mechanisms of Mn-induced neurotoxicity associated with PD remain unclear. Serpina3n is highly expressed in astrocytes and has been implicated in several neuropathologies. The role Serpina3n plays in Mn neurotoxicity and PD pathogenesis is still unknown. Here, we used wild-type and Serpina3n knockout (KO) C57BL/6 J mice with i.p. injection of 32.5 mg/kg MnCl₂ on

SUBMITTER: Hong H 

PROVIDER: S-EPMC11759460 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature