Causes of Parkinson's disease
[1] Parkinson's disease (PD) is primarily caused by the gradual degeneration of dopaminergic neurons in the region known as the substantia nigra along with other monoaminergic cell groups throughout the brainstem,[2] increased activation of microglia, and the build-up of Lewy bodies and Lewy neurites, which are proteins found in surviving dopaminergic neurons.
[19][20] The role of the SNCA gene is significant in PD because the alpha-synuclein protein is the main component of Lewy bodies, which appear as a primary biomarker in the disease.
[9][21] Missense mutations of the gene (in which a single nucleotide is changed), and duplications and triplications of the locus containing it have been found in different groups with familial PD.
[9] Level of alpha-synuclein expression correlates with disease onset and progression, with SNCA gene triplication advancing earlier and faster than duplication.
[9] Genome-wide association studies, which search for mutated alleles with low penetrance in sporadic cases, have now yielded many positive results.
[26] Incidentally, both gain-of-function and loss-of-function GBA mutations are proposed to contribute to parkinsonism through effects such as increased alpha-synuclein levels.
[26] may play a role in maintaining supply of synaptic vesicles in presynaptic terminals; may regulate release of dopamine[30] - Inactivating somatic mutations - Frequent intragenic deletions -Mostly point mutations -Deletions on C-terminus Kinase domain - Large deletion in L166P Exposure to pesticides, metals, solvents, and other toxicants has been studied as a factor in the development of Parkinson's disease.
Recent studies also reveal that individuals that sustain mild head injuries (concussions) also have an increased risk of acquiring the disease.
Evidence from epidemiological, animal, and in vitro studies suggests that exposure to pesticides increases the risk for Parkinson's disease.
[7] Carbon disulfide is a risk factor, and has been identified in industrial worker case studies and has induced parkinsonism in mice.
[non-primary source needed][45] It is mainly used in the manufacture of viscose rayon, cellophane film, rubber and carbon tetrachloride.
[43] A 2018 study found 56% increase in risk of Parkinson's disease among US military veterans suffered traumatic brain injury.
A 2023 study found that adherence to a Western dietary pattern—characterized by high consumption of red and processed meats, fried foods, high-fat dairy products, and refined grains—is associated with an increased risk of Parkinson's.
Conversely, diets rich in fruits, vegetables, whole grains, and lean proteins have been associated with a reduced risk of Parkinson's, potentially offering protective benefits.
