Affected brain regions and pathogenic factors of PD. (IMAGE)
Caption
(A) In early/mid-stage PD, the nigrostriatal pathway (indicated by red arrow) is primarily affected, leading to impaired voluntary movement control due to dopamine depletion in the striatum. During late-stage PD, three additional pathways are compromised: the mesocortical pathway (green arrow), associated with cognitive functions such as memory and motivation; the mesolimbic pathway (blue arrow), involved in emotional processing and reward perception; and the tubero-infundibular pathway (purple arrow), which regulates hormonal balance and sensory integration.
(B) The pathogenesis of PD involves three major factors: (1) aging, which accelerates mitochondrial dysfunction (2) environmental toxins (e.g., pesticides, heavy metals) that inhibit mitochondrial complex I and induce oxidative stress; and (3) genetic mutations (e.g., SNCA, LRRK2, PINK1, and Parkin) that disrupt mitochondrial quality control and autophagy.
(C) The cascade of neuronal damage begins with dopaminergic neuron degeneration in the substantia nigra, causing insufficient dopamine secretion. Mitochondrial dysfunction exacerbates this process by reducing ATP production and amplifying oxidative stress, creating a vicious cycle that further damages neurons and drives disease progression.
Credit
Tingting Liu, Jingwen Li, Haojie Wu, Junbo Qiao, Jianshe Wei
Usage Restrictions
Credit must be given to the creator. Only noncommercial uses of the work are permitted. No derivatives or adaptations of the work are permitted.
License
CC BY-NC-ND