Nicotinamide as a Foundation for Treating Neurodegenerative Disease and Metabolic Disorders

Jan 5, 2021Current neurovascular research

Nicotinamide as a Basis for Treating Brain Degeneration and Metabolic Disorders

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Abstract

More than one billion individuals worldwide are affected by neurodegenerative disorders, with additional links to metabolic disease impacting another nine hundred million.

Nicotinamide may provide protective effects against various toxic environments, including oxidative stress and excitotoxicity.
The protective effects of nicotinamide are concentration-dependent, with specific dosing required to avoid detrimental outcomes.
Biological pathways involving SIRT1, mTOR, AMPK, and FoxOs are associated with nicotinamide's protective mechanisms.
Understanding the complex biology of nicotinamide is crucial for its potential clinical application in treating neurodegenerative disorders and metabolic diseases.

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Neurodegenerative disorders impact more than one billion individuals worldwide and are intimately tied to metabolic disease that can affect another nine hundred individuals throughout the globe. Nicotinamide is a critical agent that may offer fruitful prospects for neurodegenerative diseases and metabolic disorders, such as diabetes mellitus. Nicotinamide protects against multiple toxic environments that include reactive oxygen species exposure, anoxia, excitotoxicity, ethanolinduced neuronal injury, amyloid (Aß) toxicity, age-related vascular disease, mitochondrial dysfunction, insulin resistance, excess lactate production, and loss of glucose homeostasis with pancreatic β-cell dysfunction. However, nicotinamide offers cellular protection in a specific concentration range, with dosing outside of this range leading to detrimental effects. The underlying biological pathways of nicotinamide that involve the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and mammalian forkhead transcription factors (FoxOs) may offer insight for the clinical translation of nicotinamide into a safe and efficacious therapy through the modulation of oxidative stress, apoptosis, and autophagy. Nicotinamide is a highly promising target for the development of innovative strategies for neurodegenerative disorders and metabolic disease, but the benefits of this foundation depend greatly on gaining a further understanding of nicotinamide's complex biology.

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Nicotinamide as a Foundation for Treating Neurodegenerative Disease and Metabolic Disorders

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