A review on neurodegenerative disease: The race to develop disease modifying drugs for Alzheimer’s and Parkinson’s
Author(s):
Muskan Pandey, Patel Bijal, Desai Saloni and Desai Chirag
Abstract:
Neurodegenerative disorders represent a heterogeneous group of chronic and progressively debilitating conditions that result from the gradual loss of structure and function of neurons in the central nervous system (CNS). This deterioration leads to irreversible impairments in cognition, motor control, and other vital neurological processes, frequently culminating in profound disability or death. Prominent examples include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, and Amyotrophic Lateral Sclerosis (ALS). Despite their clinical differences AD being primarily associated with memory decline and executive dysfunction, while PD is characterized by bradykinesia, tremors, and rigidity both share common pathological mechanisms. These include chronic neuroinflammation, mitochondrial dysfunction, oxidative stress due to reactive oxygen species imbalance, and abnormal protein misfolding or aggregation (such as amyloid-?, tau, and ?-synuclein). Current therapeutic strategies are largely palliative, focusing on symptomatic relief rather than halting disease progression. In AD, treatment typically involves acetylcholinesterase inhibitors (e.g., Donepezil, Galantamine) or N-methyl-D-aspartate (NMDA) receptor antagonists (Memantine), with newer interventions such as anti-amyloid monoclonal antibodies (Aducanumab, Lecanemab) being investigated to reduce amyloid plaque burden. In PD, dopamine replacement therapy with Levodopa and dopamine receptor agonists like Pramipexole and Ropinirole remain the cornerstone of management, though they do not prevent ongoing dopaminergic neuronal degeneration. Increasing evidence highlights the role of the innate immune system, particularly microglial over activation, in driving disease progression through persistent release of pro-inflammatory cytokines including tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), and interleukin-6 (IL-6). This has stimulated growing interest in the potential repurposing of Disease-Modifying Anti-Rheumatic Drugs (DMARDs), traditionally used for autoimmune conditions such as rheumatoid arthritis, as possible disease-modifying therapies. Such a shift from purely symptomatic management to immunomodulatory and neuroprotective strategies marks an emerging and promising avenue for the treatment of AD, PD, and other neurodegenerative conditions.
