The objective of this study is to elucidate the underlying neurobiological mechanisms of Amyotrophic Lateral Sclerosis (ALS) to enhance understanding of disease progression and identify potential therapeutic targets. ALS is a progressive neurodegenerative disorder characterized by the degeneration of motor neurons, leading to muscle weakness and atrophy. Despite extensive research, the precise mechanisms driving ALS pathology remain poorly understood.

ALS is a complex disease involving both genetic and environmental factors. It is marked by the selective loss of motor neurons in the brain and spinal cord, which impairs voluntary muscle movements. Previous studies have identified several key processes implicated in ALS, including oxidative stress, protein misfolding, neuroinflammation, and impaired axonal transport. Mutations in genes such as SOD1, C9orf72, and TARDBP have been associated with familial forms of ALS, providing insights into potential pathological mechanisms.

This study employed a multi-faceted approach combining molecular biology principles and human tissue analysis. We utilized transcriptomic and proteomic analyses to identify differential gene and protein expression in ALS patient tissues and transgenic mouse models. In addition, we conducted immunohistochemical studies to examine neuroinflammatory responses and neuronal cell death. Electrophysiological assessments were used to evaluate motor neuron function and integrity

Our findings reveal significant dysregulation in pathways associated with oxidative stress and protein homeostasis in ALS models. Notably, we observed increased activation of microglia and astrocytes, suggesting heightened neuroinflammatory responses. Additionally, axonal-transport disruptive mechanisms were evident. These results correlate with the clinical progression of ALS, highlighting the importance of these processes in disease pathogenesis.

This study advances our understanding of ALS by identifying critical neurobiological alterations associated with the disease. The evidence points to a complex interplay of oxidative stress, neuroinflammation, and disrupted protein homeostasis as central to ALS pathology. These insights underscore the need for therapeutic strategies that address these molecular and cellular dysfunctions.