Muscle building supplement HMB for remyelination

病理上，多发性硬化症（MS）可以通过弥漫性、离散性的存在来鉴别

Pathologically, multiple sclerosis (MS) can be identified by the presence of diffuse, discrete demyelinated areas, called plaques. Demyelination is a major feature of MS and therefore, an approach to the management of MS involves an increase in remyelination of axons, resulting in clinical improvement. Peroxisome proliferator-activated receptor β or δ (PPARβ) being highly expressed in the CNS participates in many brain functions including myelination. Being a nuclear hormone receptor, PPARβ needs ligand(s) for its activation and nuclear translocation. Therefore, identification of new nontoxic ligand of PPARβ would be very important for promoting remyelination. The β-hydroxy β-methylbutyrate (HMB) is available in local GNC stores as a muscle-building supplement in human. It is a physiological molecule that is produced in human through the metabolism of L-leucine. HMB is known to increase exercise-induced gains in muscle size and muscle strength and improve exercise performance. Our preliminary results show that HMB may bind and activate PPARβ and stimulate the maturation of oligodendroglial progenitor cells (OPCs) to oligodendrocytes (OL), myelin-producing cells in the CNS. Therefore, here, we will test an exciting hypothesis that HMB binds to the ligand- binding domain of PPARβ and that HMB and its precursor L-leucine promote maturation of OPCs and stimulate remyelination in animal models (cuprizone and experimental allergic encephalomyelitis) of CNS demyelination via PPARβ. Administrative supplement: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in humans and despite intense investigations, no effective therapy is available to halt the progression of AD. Interestingly, our preliminary results show marked demyelination in the hippocampus and cortex of postmortem AD brains as compared to age-matched control brains with no cognitive impairment. Similarly, we have seen demyelination in the hippocampus and cortex of 5XFAD mice, but not age-matched non-transgenic mice. Since the muscle building supplement HMB activates PPARβ, increases myelin-specific genes and stimulates the maturation of OPC to OL, here, in response to NOT-AG-20-034 entitled “Notice of Special Interest: Alzheimer’s-focused administrative supplements for NIH grants that are not focused on Alzheimer’s disease”, we have planned to test an exciting hypothesis that oral administration of HMB and its precursor Leu stimulates remyelination and improves cognitive functions in 5XFAD mouse model of AD via PPARβ. A positive outcome of this administrative supplement will indicate whether demyelination/remyelination is a therapeutic target in AD, enhance the possibility of promoting remyelination and improving cognitive functions in AD patients with muscle-building supplement HMB and a simple non-toxic amino acid L-leucine as primary or adjunct therapy.