Malfunctions in synaptic membrane trafficking in early pathology of Parkinson’s disease: New molecular clues

Abstract

The midbrain dopaminergic neurons of the substantia nigra and the ventral tegmental area play vital roles in the regulation of voluntary movement, emotion and reward in humans. These neurons are highly metabolic and are under constant oxidative stress. The dopaminergic neurons form extensive synaptic projections to the striatum. When these neurons start dying or when their synaptic connections fail, humans develop Parkinson´s disease. This disease is accompanied by the accumulation of toxic α-synuclein-containing protein aggregates in nigrostriatal processes. Synucleins accumulate in a majority of healthy nerve terminals in the central nervous system, but what causes the formation of pathological synuclein aggregates is unclear. Recent studies point out that the interface between membrane trafficking in the nerve terminal and the autophagy-lysosomal pathway is the site for the aggregate assembly. An urgent goal is to find therapeutic targets at early stages of the disease when neurons are still functional.

miR-185 and SEPT5 Genes May Contribute to Parkinson’s Disease Pathophysiology

“…Additionally, previous studies show that the increase in SEPT5 gene expression can lead in dopaminergic cell death through the formation of the Lewy bodies [28, 29]. In current study, the expression of normal LRRK2 increased, while most of other studies only show the increase in the kinase activity of LRRK2 due to the certain mutations [30].…”