Roots to start research in amyotrophic lateral sclerosis: molecular pathways and novel therapeutics for future

• Published in: Reviews in the neurosciences Vol. 26; no. 2; pp. 161 - 181
• Main Authors: Harikrishnareddy, Dibbanti, Misra, Shubham, Upadhyay, Sujata, Modi, Manish, Medhi, Bikash
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 01.04.2015; Walter de Gruyter GmbH
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - drug therapy; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - therapy; Animals; Antidepressants; Clinical trials; Clinical Trials as Topic; Disease; Genetic Therapy; Humans; Metabolism; motor neuron disease; Mutation; Neurons; Neuroprotective Agents - therapeutic use; Oxidative Stress; pathogenesis; Rodents; Stem Cell Transplantation; Studies; therapy; Ventilation
• ISSN: 0334-1763; 2191-0200
• DOI: 10.1515/revneuro-2014-0057

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease that rapidly progresses from mild motor symptoms to severe motor paralysis and premature death. There is currently no cure for this devastating disease; most ALS patients die of respiratory failure generally within 3–5 years from the onset of signs and symptoms. Approximately 90% of ALS cases are sporadic in nature, with no clear associated risk factors. It is reported that ALS is a complex and multifaceted neurodegenerative disease. Less is known about the key factors involved in the sporadic form of the disease. The intricate pathogenic mechanisms that target motor neurons in ALS includes oxidative stress, glutamate excitotoxicity, mitochondrial damage, protein aggregation, glia and neuroinflammation pathology, defective axonal transport, and aberrant RNA metabolism. Despite aggressive research, no therapy has been yet proven to completely reverse the core symptoms of the disease. Riluzole is the only drug approved by the Food and Drug Administration and recommended by the National Institute for Clinical Excellence so far proven to be successful against ALS and may prevent progression and extend life for a few months or so. This article provides a novel understanding in key findings of pathogenesis and interventions currently under investigation to slow disease progression in ALS.