Increasing NAD+ levels with nicotinamide mononucleotide (NMN) improves the defective clearance of damaged mitochondria caused by prion diseases, protecting these neurons from cell death.
Prion diseases, which caught the public eye due to the 2003 “mad cow disease” outbreak in the UK, are a group of chronic, fatal, neurodegenerative diseases that can infect humans and animals. As with many other neurodegenerative diseases, especially those that are age-related, prion diseases – or transmissible spongiform encephalopathies (TSEs) – involve misfolded proteins, like Alzheimer’s and Parkinson’s disease, are often affected by a persistent accumulation of damaged mitochondria in neurons.
Researchers from China Agricultural University in Beijing, China, show that two NAD+ boosting compounds protect prion disease neurons from death. Published in Cell Death & Disease, Li and colleagues show that NMN and urolithin A improve the pool of healthy mitochondria in prion disease neurons by inducing mitophagy – the process for clearing damaged mitochondria. These findings suggest that mitophagy-stimulating compounds like these compounds that boost NAD+ could be therapeutic interventions for prion diseases.
Mangled Mitochondria May Perpetuate Prion Disease
The name “prions” refers to aberrant, disease-causing agents that are transmissible and can cause improper folding of particular normal cellular proteins known as prion proteins, which are prevalent in the brain. Prion diseases, such as Creutzfeldt-Jakob disease, may occur spontaneously, be inherited, or be transmitted by contact with infected tissue, such as during a transplant or from eating contaminated meat.
While the roles of these normal prion proteins are currently being researched, it’s known that the aberrant folding of prion proteins causes brain damage and the disease’s typical signs and symptoms. Prion diseases have been shown to cause personality changes, anxiety, depression, and memory loss, usually within a few months, and many people lapse into coma. Prion illnesses generally advance quickly and are invariably deadly, but how this rapid neurodegeneration occurs remains a bit of a mystery.
A persistent accumulation of damaged mitochondria in neurons has been associated with aging and neurodegenerative diseases, including prion diseases. Mitophagy, one of the intracellular mitochondrial quality control pathways, can selectively remove damaged mitochondria, which may be associated with the accumulation of damaged mitochondria in prion diseases. Many studies have reported the importance of PINK1-parkin dependent mitophagy pathways in neurons: PINK1-parkin forms a signal transduction pathway that labels damaged mitochondria for elimination.