Article: Nicotinamide Riboside and Necroptosis Inhibition Improve ALS: Preclinical Findings

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Amyotrophic Lateral Sclerosis (ALS) Neurological Health Preclinical

Nicotinamide Riboside and Necroptosis Inhibition Improve ALS: Preclinical Findings

Synopsis

TBK1 loss-of-function mutations linked to amyotrophic lateral sclerosis (ALS) were modeled in zebrafish using CRISPR and morpholino knockdown. Both approaches caused early motor deficits, motor neuron degeneration, and increased lethality. Metabolomics revealed severe disruptions in nicotinamide metabolism, and treatment with nicotinamide riboside (NR) restored locomotor behavior in tbk1 mutants. Proteomics showed elevated inflammatory proteins and strong activation of necroptosis, a programmed cell-death pathway. Blocking necroptosis with necrosulfonamide significantly improved survival. Cross-species comparison with TBK1-mutant human motor neurons identified shared ALS-related pathway disruptions, including impaired nuclear–cytoplasmic transport and elevated STAT1. These findings highlight metabolic failure and necroptosis as key drivers of pathology in TBK1-associated ALS and support NR and necroptosis inhibition as potential therapeutic strategies.

Journal

Cell Death Discovery

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Kidney Disease

Nicotinamide Riboside Protects Against Chronic Kidney Disease by Boosting Metabolism: Preclinical Findings

SynopsisChronic kidney disease (CKD) impairs kidney metabolism, including fatty acid breakdown, and is linked to low NAD+ levels. This study tested nicotinamide riboside (NR), a precursor of NAD+, ...

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Cellular Health

Nicotinamide Riboside and NMN Boost NAD+ Through Microbiota Conversion: Preclinical Findings

Synopsis Using NAD+ metabolomics in mice, this study found that nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are not directly absorbed intact in large amounts. Instead, most or...

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