From Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders

Abstract

Neurodegenerative diseases (NDs), like amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD), primarily affect the central nervous system, leading to progressive neuronal loss and motor and cognitive dysfunction. However, recent studies have revealed that muscle tissue also plays a significant role in these diseases. ALS is characterized by severe muscle wasting as a result of motor neuron degeneration, as well as alterations in gene expression, protein aggregation, and oxidative stress. Muscle atrophy and mitochondrial dysfunction are also observed in AD, which may exacerbate cognitive decline due to systemic metabolic dysregulation. PD patients exhibit muscle fiber atrophy, altered muscle composition, and α-synuclein aggregation within muscle cells, contributing to motor symptoms and disease progression. Systemic inflammation and impaired protein degradation pathways are common among these disorders, highlighting muscle tissue as a key player in disease progression. Understanding these muscle-related changes offers potential therapeutic avenues, such as targeting mitochondrial function, reducing inflammation, and promoting muscle regeneration with exercise and pharmacological interventions. This review emphasizes the importance of considering an integrative approach to neurodegenerative disease research, considering both central and peripheral pathological mechanisms, in order to develop more effective treatments and improve patient outcomes.

Keywords: muscle; neurodegenerative diseases; therapy.

Figure 1

A schematic representation of skeletal muscle structure. The image was created with the use of Servier Medical Art modified templates, licensed under a Creative Common Attribution 3.0 Unported License (https://smart.servier.com, accessed on 28 August 2024).

Figure 2

A schematic representation of the accumulation of ROS leading to mitochondrial dysfunction and cellular damage. This cascade of events results in muscle atrophy and weakness. The image was created with the use of Servier Medical Art modified templates, licensed under a Creative Common Attribution 3.0 Unported License (https://smart.servier.com, accessed on 28 August 2024).

Figure 3

The aggregates of α-synuclein caused by alterations in protein degradation pathways promote the muscle cell alterations typically found in PD patients. The image was created with the use of Servier Medical Art modified templates, licensed under a Creative Common Attribution 3.0 Unported License (https://smart.servier.com, accessed on 28 August 2024).