α-Synuclein interacts with the switch region of Rab8a in a Ser129 phosphorylation-dependent manner.

Alpha-synuclein (αS) misfolding is associated with Parkinson's disease (PD) but little is known about the mechanisms underlying αS toxicity. Increasing evidence suggests that defects in membrane transport play an important role in neuronal dysfunction. Here we demonstrate that the GTPase Rab8a interacts with αS in rodent brain.

Structural comparison of mouse and human α-synuclein amyloid fibrils by solid-state NMR.

Fibrillar α-synuclein (AS) is the major component of Lewy bodies, the pathological hallmark of Parkinson's disease. Mouse AS (mAS) aggregates much faster than human AS (hAS), although mAS differs from hAS at only seven positions in its primary sequence. Currently, little is known about the site-specific structural differences between mAS and hAS fibrils.

Structures behind the amyloid aggregation of α-synuclein: an NMR based approach.

The misfolding of proteins into a toxic conformation is proposed to be at the molecular foundation of a number of neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Evidence that α-synuclein amyloidogenesis plays a causative role in the development of Parkinson's disease is furnished by a variety of genetic, neuropathological and biochemical studies. There is a major interest in understanding the structural and toxicity features of the various species populated along the aggregation pathway of this protein.

Structural and mechanistic basis behind the inhibitory interaction of PcTS on alpha-synuclein amyloid fibril formation.

The identification of aggregation inhibitors and the investigation of their mechanism of action are fundamental in the quest to mitigate the pathological consequences of amyloid formation. Here, characterization of the structural and mechanistic basis for the antiamyloidogenic effect of phthalocyanine tetrasulfonate (PcTS) on alpha-synuclein (AS) allowed us to demonstrate that specific aromatic interactions are central for ligand-mediated inhibition of amyloid formation. We provide evidence indicating that the mechanism behind the antiamyloidogenic effect of PcTS is correlated with the trapping of prefibrillar AS species during the early stages of the assembly process.