α–Synuclein aggregation and therapeutic approarch

Abstract

α–Synucleinopathies including Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are neurodegenerative disorders characterized by the abnormal accumulation of α–synuclein (αS) aggregates in the nervous system. In these disorders, misfolded, phosphorylated, and insolubilized αS accumulates in the neuronal cytoplasm as Lewy bodies in PD and DLB, and in the oligodendroglial cytoplasm as glial cytoplasmic inclusion in MSA, and spreads progressively.

Although a lot of drugs have been developed for PD since the efficacy of levodopa was confirmed, they are limited to symptomatic treatment and no disease modifying therapy (DMT) has been developed. However, advances in genetics and cell biology have accumulated a lot of findings on the molecular pathogenesis of αS and neurotoxicity, and efforts are underway to develop DMT for α–synucleinopathies.