Parkinson’s disease (PD) is a progressive neurological movement disorder manifested by motor and non-motor disturbances that are brought about by degeneration of dopaminergic (DAergic) neurons in the substantia nigra (SN), causing a decline in dopamine (DA) levels in the striatum. Pharmacological and surgical treatment of PD are often ineffective, cause severe side effects, and the benefits seen decrease with disease progression; therefore, there is a need to seek new therapies. Physical activity (PA), which includes exercise, is able to improve many systems in the body, including motor and cognitive function, and may serve as a viable option for remedy of PD. Due to many limitations, human studies are unlikely to explain whether such intervention may be neuroprotective in PD patients; therefore, the use of animal models is imperative. PA in animal models of PD has neuroprotective effects on DAergic neurons and current hypotheses infer a central role of neurotrophic factors (NTFs); however, the exact mechanisms of their action have yet to be elucidated. In the present review, studies will be discussed that highlight how PA increases NTF mobilization leading to protection of DAergic neurons and improved motor performance. Furthermore, this review will explore NTF influence in several postulated aberrant cellular processes where intervention could be made to treat PD, including neuroplasticity and synaptic transmission, angiogenesis and vasodilation, mitochondrial dysfunction through oxidative stress and protein aggregation, and neuroinflammation
