Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by a range of motor and non-motor symptoms. While traditionally viewed as a single entity, recent research suggests PD comprises various subtypes with distinct clinical presentations, genetic factors, and potential environmental triggers.
Beyond the classic motor symptoms like tremors, rigidity, and slow movement (bradykinesia), non-motor manifestations often precede the onset of motor issues. These can include rapid eye movement sleep behavior disorder (RBD), loss of smell (anosmia), constipation, and depression. As PD progresses, cognitive impairment and dysfunction of the autonomic nervous system (dysautonomia) frequently emerge, often dominating the later stages of the disease.
At the molecular level, several key pathogenic mechanisms contribute to PD development. Misfolding and aggregation of the protein α-synuclein, mitochondrial dysfunction, impaired protein clearance (linked to deficiencies in the ubiquitin-proteasome and autophagy-lysosomal systems), neuroinflammation, and oxidative stress all play significant roles. The intricate interplay of these mechanisms affects various neurotransmitter pathways, including dopaminergic, noradrenergic, glutamatergic, serotonergic, and adenosine pathways. Understanding these pathways provides insights into the diverse clinical symptoms observed in PD and opens avenues for exploring alternative therapeutic approaches beyond traditional dopamine replacement therapies.
One of the major hurdles in developing neuroprotective therapies for PD is the lack of sensitive and reliable biomarkers to track disease progression. Currently, promising research focuses on immunotherapies, such as vaccines or monoclonal antibodies targeting aggregated α-synuclein, as well as strategies aimed at preventing protein aggregation or enhancing protein clearance. These approaches are currently being evaluated in clinical trials.
Furthermore, there is cautious optimism surrounding the potential of glucagon-like peptide-1 receptor agonists, gene-targeted therapies (e.g., modifiers of GBA or LRRK2 genes), and other disease-modifying drugs. These emerging therapies, along with new symptomatic medications, innovative drug delivery systems, and novel surgical interventions, offer hope for improved outcomes and prognosis for individuals living with PD. Further research and clinical trials are crucial to validate these promising avenues and bring more effective treatments to patients.
