Identification of RBMX as a splicing regulator in Parkinsonian mimetic induced alternative splicing of α-synuclein.

α-Synuclein (α-syn) plays a precipitating role in Parkinson's disease (PD) due to its tendency to form oligomers and fibrils. The presence of smaller isoforms of α-syn was widely noticed in the affected brain regions of PD patients. 112-synuclein (112-syn) which lacks exon-5, possess enhanced aggregation propensity and forms intracellular inclusions.

Identification of an Alternatively Spliced α-Synuclein Isoform That Generates a 41-Amino Acid N-Terminal Truncated Peptide, 41-syn: Role in Dopamine Homeostasis.

The presynaptic protein, α-synuclein (α-syn), has been shown to play a crucial role in multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), and dementia with Lewy bodies (DLB). The three major domains of α-syn protein were shown to govern its membrane interaction, protein fibrillation, and chaperone activity. So far, four different alternatively spliced isoforms of α-syn, which lack either exon 3 (syn-126) or exon 5 (syn-112) or both (syn-98) resulting in altered function of the proteins, have been identified.

The unintended mitochondrial uncoupling effects of the FDA-approved anti-helminth drug nitazoxanide mitigates experimental parkinsonism in mice.

Mitochondria play a primary role in the pathophysiology of Parkinson's disease (PD), and small molecules that counteract the initial stages of disease may offer therapeutic benefit. In this regard, we have examined whether the off-target effects of the Food and Drug Administration (FDA)-approved anti-helminth drug nitazoxanide (NTZ) on mitochondrial respiration could possess any therapeutic potential for PD. Results indicate that MPP-induced loss in oxygen consumption rate (OCR) and ATP production by mitochondria were ameliorated by NTZ in real time by virtue of its mild uncoupling effect.