Year-end Sale % OFF 
Abstract
Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease of the motor system. It is characterized by the degeneration of both upper and lower motor neurons, which leads to muscle weakness and paralysis. ALS is incurable and has a bleak prognosis, with median survival of 3–5 years after the initial symptomatology. In ALS, motor neurons gradually degenerate and die. Many features of mitochondrial dysfunction are manifested in neurodegenerative diseases, including ALS. Mitochondria have shown to be an early target in ALS pathophysiology and contribute to disease progression. Disruption of their axonal transport, excessive generation of reactive oxygen species, disruption of the mitochondrial structure, dynamics, mitophagy, energy production, calcium buffering and apoptotic triggering have all been directly involved in disease pathogenesis and extensively reported in ALS patients and animal model systems. Alterations in energy production by motor neurons, which severely limit their survival capacity, are tightly linked to the redox status and mitochondria. The present review focuses on this link. Placing oxidative stress as a main pathophysiological mechanism, the molecular interactions and metabolic flows involved are analyzed. This leads to discussing potential therapeutic approaches targeting mitochondrial biology to slow disease progression.
Highlights
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease [1] characterized by a gradual loss of upper and lower motor neurons (MNs)
Alterations in the structure and function of mitochondria have been postulated as the core in the pathophysiology of different neurodegenerative diseases [12] and are evident in MNs affected by ALS [13,14,15,16]
In a recent pilot study, we demonstrated that the association of pterostilbene (PT, a natural antioxidant polyphenol) and nicotinamide riboside (NR, a vitamin B3 derivative and an NAD+ booster that supports the activity of Sirts) was able to slow the progressive decline in functionality, strength and lung function in ALS patients [121]
Summary
ALS is a rapidly progressive neurodegenerative disease [1] characterized by a gradual loss of upper and lower motor neurons (MNs). The appearance of abnormal muscle movements (spasms, jerks, cramps or weakness) in the hands and feet causes difficulty in lifting, walking or using one’s hands to dress, wash and button clothing. It can start with an abnormal loss of muscle mass or body weight [2,3]. The progression of the disease is normally asymmetric Sometimes, it is very slow, developing over the years and having periods of stability with a variable degree of disability. Whatever the real course of the pathophysiology, many of the abovementioned factors directly or indirectly converge in the mitochondria
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
