Abstract
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the selective degeneration of motor neurons in the brain and spinal cord. This devastating condition affects approximately 2-3 individuals per 100,000 population globally, with a median survival time of 3-5 years from symptom onset. The disease presents with heterogeneous clinical manifestations, ranging from limb-onset weakness to bulbar dysfunction, ultimately leading to respiratory failure and death. While the exact etiology remains incompletely understood, current evidence suggests a complex interplay of genetic, environmental, and cellular mechanisms contributing to motor neuron degeneration. This comprehensive review examines the multifaceted nature of ALS, including its underlying pathophysiology, clinical presentations, diagnostic challenges, and current therapeutic approaches. Despite significant advances in understanding the molecular basis of ALS, treatment options remain limited, with only a few FDA-approved medications providing modest clinical benefits. Recent developments in gene therapy, stem cell research, and novel pharmacological targets offer promising avenues for future therapeutic interventions.
Keywords
Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Neurodegeneration, Riluzole, Edaravone, Gene Therapy
Introduction
Amyotrophic Lateral Sclerosis, first described by French neurologist Jean-Martin Charcot in 1869, represents one of the most challenging neurodegenerative diseases facing modern medicine. The term "amyotrophic" refers to muscle atrophy, while "lateral sclerosis" describes the hardening of lateral columns in the spinal cord due to gliosis following motor neuron death. ALS is characterized by the progressive degeneration of both upper motor neurons (UMNs) in the motor cortex and lower motor neurons (LMNs) in the brainstem and spinal cord, leading to muscle weakness, atrophy, and eventual paralysis. The global burden of ALS continues to grow, with increasing recognition of the disease's impact on patients, families, and healthcare systems. The heterogeneous nature of ALS presentation and progression has led to extensive research efforts aimed at understanding its underlying mechanisms and developing effective therapeutic strategies. This review synthesizes current knowledge regarding ALS etiology, clinical manifestations, and treatment approaches, while highlighting areas requiring further investigation.
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Arnab Roy
Corresponding author
Sai Nath University, Ranchi, Jharkhand-835219, India
Shruti Kumari
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Bindu Kumari
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Abhinav Kumar
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Divya Kumari
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Indu Sharma
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Ashish Kumar
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Balram Mahto
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Abhinav Keshri
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Niraj Kumar
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Manvi Kumari
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Priyanka Singh
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Keshav Kumar
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Abhijit Kumar
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Aman Kumar
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Suman Roy
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Ankita Singh
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Shruti Kumari, Bindu Kumari, Abhinav Kumar, Divya Kumari, Indu Sharma, Ashish Kumar, Balram Mahto, Abhinav Keshri, Niraj Kumar, Manvi Kumari, Priyanka Singh, Keshav Kumar, Abhijit Kumar, Aman Kumar, Suman Roy, Ankita Singh, Arnab Roy*, Amyotrophic Lateral Sclerosis: A Comprehensive Review of Pathophysiology, Clinical Manifestations and Current Treatment Paradigms, Int. J. Sci. R. Tech., 2025, 2 (8), 46-56. https://doi.org/10.5281/zenodo.16751522
10.5281/zenodo.16751522
