Leptin as a potential neuroprotective target in Parkinson's Disease: Exploring its role in Neuroinflammation, oxidative Stress, and dopaminergic neurodegeneration.

Parkinson's disease (PD) is the second most commonneurodegenerative disease, characterized bybradykinesia, resting tremor, stiffness, and postural instabilityresulting due to the progressive loss ofdopaminergic neurons in the substantia nigra (SN). The pathophysiology of PDis extremely complex and involves mitochondrial dysfunction, oxidative stress, neuroinflammation, and disruption of protein homeostasis. Its progression is affected by both environmental and genetic factors, including mutations in the alpha-synuclein (SNCA), PTEN-induced kinase 1 (PINK1), and leucine-rich repeat kinase 2 (LRRK2) genes. Leptin, primarily secreted by the adipose tissue, has garnered significant interest for its involvement in neuroprotective mechanisms and potential role in the progression of PD. Its receptors located in the SN and hippocampus region indicate its role in neuronal survival and function. The role of leptin in the central nervous system (CNS) highlights its impact on neuroinflammation, oxidative stress, and synaptic plasticity. Recent studies indicate that through activation of Janus kinase/signal transducer and activator of transcription (JAK2/STAT3) and the phosphoinositide 3 kinase (PI3 K)/Akt pathways, leptin may exert a neuroprotective effect by preventing the degeneration of dopaminergic neurons, which marked as the hallmark in the pathophysiology of PD. Additionally, leptin's interaction with neurotrophic factors and its ability to enhance synaptic plasticity highlight its vital role in preserving neuronal health. This review summarizes the role of leptin as a neuroprotective mechanism in PD and explores its potential role as a therapeutic target for treatment to enhance neuroprotection and clinical outcome, by addressing the neurodegenerative characteristics associated with PD.