Neurodegenerative disorders represent a group of chronic, progressive conditions characterised by irreversible damage to and dysfunction of neurons. These disorders are characterised by the gradual degeneration of specific neuronal populations, leading to cognitive, motor, and/or behavioural impairments1. The most prevalent and well-studied neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, although other conditions, such as frontotemporal dementia and multiple system atrophy, also fall under this category. The exact causes of these disorders remain poorly understood, but they are commonly associated with abnormal protein aggregation, genetic mutations, and mitochondrial dysfunction, among other pathological mechanisms2. The global prevalence of neurodegenerative disorders is increasing due to the ageing population, making them a growing public health concern. Alzheimer's disease, for example, is the most common form of dementia, affecting an estimated 50 million people worldwide. Parkinson's disease affects approximately 10 million people, whereas Huntington's disease and ALS impact smaller but still significant portions of the population3. The societal burden of these diseases is immense, not only because of the healthcare costs associated with their management but also because of the emotional and social toll on patients, families, and caregivers. As neurodegenerative diseases progress, individuals typically lose the ability to perform everyday tasks, and their dependence on others for basic care increases, significantly reducing their quality of life4. Despite extensive research efforts, the pharmacological management of neurodegenerative disorders remains limited, with a primary focus on symptom management rather than modifying disease progression. Current treatments for AD, PD, HD, and ALS are often insufficient and provide only modest improvements in symptom control5. The lack of effective, disease-modifying therapies remains one of the major challenges in neurodegenerative medicine. For example, in Alzheimer's disease, acetylcholinesterase inhibitors and NMDA receptor antagonists offer only symptomatic relief and do not slow disease progression. Similarly, Parkinson's disease treatments, such as levodopa, can alleviate motor symptoms but fail to address the underlying neurodegenerative process
- Pathophysiology of Neurodegenerative Disorders
Neurodegenerative disorders share common pathogenic mechanisms that drive the progressive degeneration of neurons, although each condition also presents distinct pathophysiological features. These diseases are characterised primarily by accumulating misfolded proteins, oxidative stress, neuroinflammation, and mitochondrial dysfunction, impairing cellular processes and leading to neuronal death. Elucidating these shared mechanisms is crucial for identifying potential pharmacological targets6,7.
Mukund Pache*
Hrutuja Kedar
Snehal Kond
Pratik Jadhav
Tejashree Kedar
10.5281/zenodo.15074000