Some Immune Mechanisms of Parkinson's Disease

Neurodegenerative diseases, which predominantly occur in advanced age, are characterized by progressive neuronal loss, disruption of cellular homeostasis, and activation of several immune-related mechanisms. Among these, Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. Despite extensive research, its pathophysiology remains incompletely understood, and no curative therapy is currently available. Multiple cellular and molecular mechanisms are implicated in the development of PD. Abnormal protein aggregation, particularly of α-synuclein, mitochondrial dysfunction with impaired energy metabolism, and oxidative stress leading to DNA, lipid, and protein damage represent central pathogenic processes. Endoplasmic reticulum (ER) stress, disturbances in protein folding, and dysfunction of the ubiquitin-proteasome system further promote neuronal injury. Moreover, microglial activation and chronic neuroinflammation, together with excitotoxicity and apoptotic pathways, accelerate the degeneration of dopaminergic neurons. Heat shock proteins, although primarily protective, are also critically involved in the regulation of protein homeostasis and apoptotic signaling. These mechanisms, when considered collectively, not only explain the complexity of neuronal loss in PD but also highlight their potential as therapeutic targets. In vitro models and cell culture studies provide valuable insights into these pathways, supporting the development of novel neuroprotective and disease-modifying strategies. As the global prevalence of PD is projected to reach nearly 13 million by 2040, understanding the interplay of immune-mediated mechanisms is essential for identifying preventive approaches and improving patient outcomes. Current pharmacological therapies such as L-DOPA remain effective for symptom control, yet future advances depend on translating mechanistic knowledge into clinically applicable interventions.