Parkinson's disease is caused by a combination of genetic, environmental, and aging-related factors, although the exact cause remains unknown. The primary pathological feature is the loss of dopamine-producing nerve cells in a brain region called the substantia nigra, which leads to the characteristic motor symptoms of the disease

. Genetics:
About 10-30% of Parkinson's risk is attributed to genetics, with several gene mutations (such as GBA, LRRK2, PRKN, SNCA) identified that increase susceptibility. However, not everyone with these mutations develops Parkinson's, indicating that other factors also contribute

. Environmental Factors:
Exposure to certain environmental toxins, such as pesticides (e.g., paraquat, rotenone), herbicides, and industrial solvents, has been linked to an increased risk of Parkinson's. Head injuries and exposure to toxins like MPTP (a contaminant found in some illicit drugs) have also been implicated. Conversely, some factors like smoking and caffeine consumption have been associated with a lower risk, though these are not recommended as preventive measures

. Aging:
Age is the greatest risk factor for Parkinson's disease. As people age, their cells become more vulnerable to damage, and gene expression changes may trigger the cellular processes that lead to Parkinson's

. Hypotheses on Disease Progression:

• The prion hypothesis suggests that misfolded alpha-synuclein protein aggregates spread between neurons, driving disease progression

• Braak's hypothesis proposes that Parkinson's may begin outside the brain, possibly triggered by an unknown pathogen entering through the nasal or digestive systems and spreading to the brain

In summary, Parkinson's disease arises from a complex interplay of genetic predisposition, environmental exposures, and aging processes that lead to the degeneration of dopamine-producing neurons in the brain