Fig. (1).

Graphical representation of overall pathophysiologies underlying ALS. The figure shows various disease mechanisms that are involved in motor neuron degeneration. Protein aggregation: Impaired proteostasis leads to aberrant protein aggregation, which may be due to the overload of the proteasome system and reduced autophagy. Glutamate excitotoxicity: Mutant EAAT2 (glutamate transporter) leads to accumulation of glutamate, which in turn hyperstimulates glutamate receptors, ultimately leading to extreme calcium influx. Neuroinflammation: Activation of astrocytes and microglia lead to more toxic molecule secretion as compared to neuroprotective molecules. Apoptosis: Motor neurons undergo apoptosis, thus, leading to neurodegeneration. Mitochondrial dysfunction: Mutated proteins mislocalize to mitochondria, thus, interfering with its normal functioning. Axonal degeneration: Changes in cytoskeletal organization, axonal transport and axonal outgrowth led to axonal degeneration, which result in axonal retraction from neuromuscular junction. Reproduced from ‘International Journal of Molecular Sciences’, Volume 23, authored by Sever B et al. [12] Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis. Copyright © 2022 by the authors. Published by MDPI.; open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).