Parkinson's disease (PD) is a neurodegenerative disorder starting with motor symptoms, resulting from the death of dopamine-generating neurons in the substantia nigra. The neurodegeneration has been recently attributed to misfolded α-synuclein aggregates. Early in the course of the disease, the most obvious symptoms are shaking, rigidity, slowness of movement and gait difficulty. Later, cognitive deficits become more obvious. Parkinson's disease affects people over the age of 50.
The pathology of the disease is characterized by the accumulation of α-synuclein in Lewy bodies in neurons, and by dopamine reduction produced in the substantia nigra. The anatomical distribution of the Lewy bodies appears to be related to the degree of the clinical symptoms of the individual.
Scientific literature has recently documented that misfolded α-synuclein, e.g. in a fibrillar form, can induce 'spreading' of α-synuclein aggregation in rodents. This implies that the presence of misfolded α-synuclein can induce further misfolding in adjacent neurons. The mechanism is internationally agreed to be mediated by misfolded protein, e.g. fibrillar forms, predominately consisting of β-sheet structures, via 'protein structure induction' in unfolded and non-toxic monomers to spread the disease in a prion-like mechanism. Together with e.g. Alzheimer’s disease, Huntington’s disease, PD is now called a proteopathic neurodegenerative disease.
“Structural and functional characterization of two alpha-synuclein strains”; Luc Bousset, Laura Pieri, Gemma Ruiz-Arlandis, Julia Gath, Poul Henning Jensen, Birgit Habenstein, Karine Madiona, Vincent Olieric, AnjaBöckmann, Beat H. Meie and Ronald Melki; 2013; Nat. Commun. 4:2575 doi: 10.1038/ncomms3575
“Addition of exogenous α-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous a-synuclein to Lewy body and Lewy neurite–like aggregates”; Laura A. Volpicelli-Daley, Kelvin C. Luk and Virginia M.-Y. Lee; 2014; Nature Protocols;
“Definition of a Molecular Pathway Mediating α-Synuclein Neurotoxicity”; Jacqueline Burré, Manu Sharma, and Thomas C. Südhof; 2015; The Journal of Neuroscience, 35(13):5221–5232