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Neurotherapeutics : the Journal of the... Jul 2023Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence... (Review)
Review
Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence has posited niacin as a promising therapeutic for several neurological disorders. In this review, we discuss the biochemistry of niacin, including its homeostatic roles in NAD supplementation and metabolism. Niacin also has roles outside of metabolism, largely through engaging hydroxycarboxylic acid receptor 2 (Hcar2). These receptor-mediated activities of niacin include regulation of immune responses, phagocytosis of myelin debris after demyelination or of amyloid beta in models of Alzheimer's disease, and cholesterol efflux from cells. We describe the neurological disorders in which niacin has been investigated or has been proposed as a candidate medication. These are multiple sclerosis, Alzheimer's disease, Parkinson's disease, glioblastoma and amyotrophic lateral sclerosis. Finally, we explore the proposed mechanisms through which niacin may ameliorate neuropathology. While several questions remain, the prospect of niacin as a therapeutic to alleviate neurological impairment is promising.
Topics: Humans; Niacin; Amyloid beta-Peptides; Pellagra; Nervous System Diseases; Alzheimer Disease; Neurology
PubMed: 37084148
DOI: 10.1007/s13311-023-01376-2 -
Antioxidants & Redox Signaling Dec 2023The remarkable geometry of the axon exposes it to unique challenges for survival and maintenance. Axonal degeneration is a feature of peripheral neuropathies, glaucoma,... (Review)
Review
The remarkable geometry of the axon exposes it to unique challenges for survival and maintenance. Axonal degeneration is a feature of peripheral neuropathies, glaucoma, and traumatic brain injury, and an early event in neurodegenerative diseases. Since the discovery of Wallerian degeneration (WD), a molecular program that hijacks nicotinamide adenine dinucleotide (NAD) metabolism for axonal self-destruction, the complex roles of NAD in axonal viability and disease have become research priority. The discoveries of the protective Wallerian degeneration slow (Wld) and of sterile alpha and TIR motif containing 1 (SARM1) activation as the main instructive signal for WD have shed new light on the regulatory role of NAD in axonal degeneration in a growing number of neurological diseases. SARM1 has been characterized as a NAD hydrolase and sensor of NAD metabolism. The discovery of regulators of nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) proteostasis in axons, the allosteric regulation of SARM1 by NAD and NMN, and the existence of clinically relevant windows of action of these signals has opened new opportunities for therapeutic interventions, including SARM1 inhibitors and modulators of NAD metabolism. Events upstream and downstream of SARM1 remain unclear. Furthermore, manipulating NAD metabolism, an overdetermined process crucial in cell survival, for preventing the degeneration of the injured axon may be difficult and potentially toxic. There is a need for clarification of the distinct roles of NAD metabolism in axonal maintenance as contrasted to WD. There is also a need to better understand the role of NAD metabolism in axonal endangerment in neuropathies, diseases of the white matter, and the early stages of neurodegenerative diseases of the central nervous system. 39, 1167-1184.
Topics: Humans; Wallerian Degeneration; NAD; Peripheral Nervous System Diseases; Axons; Neurodegenerative Diseases
PubMed: 37503611
DOI: 10.1089/ars.2023.0350 -
Nutrients Jun 2023The oxidized form of nicotinamide adenine dinucleotide (NAD+) is a critical metabolite for living cells. NAD+ may act either as a cofactor for many cellular reactions as... (Review)
Review
The oxidized form of nicotinamide adenine dinucleotide (NAD+) is a critical metabolite for living cells. NAD+ may act either as a cofactor for many cellular reactions as well as a coenzyme for different NAD+-consuming enzymes involved in the physiological homeostasis of different organs and systems. In mammals, NAD+ is synthesized from either tryptophan or other vitamin B3 intermediates that act as NAD+ precursors. Recent research suggests that NAD+ precursors play a crucial role in maintaining the integrity of the gut barrier. Indeed, its deficiency has been associated with enhanced gut inflammation and leakage, and dysbiosis. Conversely, NAD+-increasing therapies may confer protection against intestinal inflammation in experimental conditions and human patients, with accumulating evidence indicating that such favorable effects could be, at least in part, mediated by concomitant changes in the composition of intestinal microbiota. However, the mechanisms by which NAD+-based treatments affect the microbiota are still poorly understood. In this context, we have focused specifically on the impact of NAD+ deficiency on intestinal inflammation and dysbiosis in animal and human models. We have further explored the relationship between NAD+ and improved host intestinal metabolism and immunity and the composition of microbiota in vivo. Overall, this comprehensive review aims to provide a new perspective on the effect of NAD+-increasing strategies on host intestinal physiology.
Topics: Animals; Humans; Gastrointestinal Microbiome; NAD; Dysbiosis; Niacinamide; Inflammation; Mammals
PubMed: 37447318
DOI: 10.3390/nu15132992 -
The South African Journal of Psychiatry... 2023The case report depicts the complex interplay between mental and physical illness and contests the notion of mind-body dualism in medicine. It emphasises the importance...
INTRODUCTION
The case report depicts the complex interplay between mental and physical illness and contests the notion of mind-body dualism in medicine. It emphasises the importance of holistic management of patients and the misnomer of schizophrenia as a purely mental illness.
PATIENT PRESENTATION
Mr S is a 35-year-old male who presented to a South African specialist psychiatric hospital via the forensic system. He had multiple physical symptoms involving the abdominal, haematological, dermatological and neurological systems, in addition to an eight year duration of untreated psychosis with a marked decline in cognition and functioning.
MANAGEMENT AND OUTCOME
An extensive medical examination during his admission excluded conditions such as early onset dementia, Huntington's disease, pellagra, Wilson's disease, autoimmune encephalitis and substance-related complications. A definitive diagnosis of schizophrenia was made, and both physical and psychiatric symptoms responded well to the administration of an antipsychotic resulting in an eventual discharge from the hospital.
CONCLUSION
Mind-body dualism can result in a delayed diagnosis of schizophrenia and subsequent increased duration of untreated psychosis and other complications.
CONTRIBUTION
This case emphasises the flaws of mind-body dualism, and the interplay of mental and physical illness.
PubMed: 37795458
DOI: 10.4102/sajpsychiatry.v29i0.2081 -
Cureus Oct 2023This case report documents a rare occurrence of pellagra in a chronic alcoholic individual, characterized by a pruritic rash and gastrointestinal symptoms. The patient,...
This case report documents a rare occurrence of pellagra in a chronic alcoholic individual, characterized by a pruritic rash and gastrointestinal symptoms. The patient, a Caucasian male in his 60s, with a history of alcohol use disorder, presented with worsening skin lesions and non-bloody diarrhea. Laboratory findings revealed significant deficiencies in niacin and related metabolites, confirming the diagnosis. Prompt initiation of niacin supplementation, dietary adjustments, and supportive care led to notable improvements. This case shows the critical importance of recognizing pellagra in chronic alcoholism, emphasizing the triad of symptoms - rash, diarrhea, and malnutrition - as key diagnostic markers. Early intervention holds the potential to significantly enhance the patient's well-being and prevent disease progression.
PubMed: 38034227
DOI: 10.7759/cureus.47909