A small number of Parkinson’s disease cases are inherited and caused by mutations in specific genes.[1] However, the majority of Parkinson’s cases occur in people without any known family history, and the cause of disease onset isn’t clear. Observational studies have implicated possible exposure to toxic chemicals such as pesticides or heavy metals as a possible contributing factor, and many of these agents are able to cause Parkinson’s-like symptoms in animal models.[2]
Although the cause of neuron death isn’t currently understood, the following pathological mechanisms have been implicated:[3][4][5]
- Dysfunctional proteostasis, which is the regulation of proteins. In people with Parkinson’s, the protein alpha-synuclein tends to form toxic, insoluble aggregates that accumulate in brain cells, contributing to the pathology. Cellular processes such as autophagy, a process that helps to break down and clear out damaged, misfolded proteins are also disrupted.
- Pathological changes in mitochondrial function and calcium regulation
- Increased levels of oxidative stress and neuroinflammation
References
- ^Parkinson disease. MedlinePlus. Bethesda (MD): National Library of Medicine (US); updated 2012 May 1; cited 2023 Jan. 31
- ^Goldman SMEnvironmental toxins and Parkinson's disease.Annu Rev Pharmacol Toxicol.(2014)
- ^Michel PP, Hirsch EC, Hunot SUnderstanding Dopaminergic Cell Death Pathways in Parkinson Disease.Neuron.(2016-May-18)
- ^Leonidas Stefanisα-Synuclein in Parkinson's diseaseCold Spring Harb Perspect Med.(2012 Feb)
- ^Maiti P, Manna J, Dunbar GLCurrent understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments.Transl Neurodegener.(2017)