Exploratory study of sublimed sulfur, in cognitively normal subjects and in Alzheimer’s dementia (AD) subjects: implications for Sulfur targeting Hydrogen sulfide (H2S)/Homocysteine (Hcy) and beta-galactosidase (GALAC)/Autophagy Signaling in AD

Abstract

Introduction: There is mounting evidence to suggest that hyper-homocysteinemia (eHct) correlates with cognitive decline severity and cortical atrophy in AD. Hydrogen Sulfide (H 2 S) exerts neuroprotection through regulating Homocysteine (eHcy) signaling. Elemental sulfur can mediate H 2 S neuroprotection through the trans-sulfuration pathway and correct the the dysregulation of H 2 S /Hct signaling in AD. Sublimed Sulfur, formulated as SULMEDOL and approved for the treatment of lactose intolerance, activates gut beta-galactosidase (GALAC). We repurpose Sulmedol from lactose intolerance to likely CNS effect, since gut GALAC cross-talks with senescence-related GALAC expression in the brain. In view of the known regulatory function of GALAC in CNS endosomal-lysosomal autophagy system , we propose that SULMEDOL may rescue aberrant autophagy in AD.

Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease

“…However, Park et al showed that serum P levels negatively correlate with cerebral Aβ deposition [77]. To our knowledge, no other study analyzed S levels in AD patients, although the intake of sublimed sulfur was suggested to be protective in AD [78]. Most studies analyzed sulfur-containing compounds in AD patients (reviewed in [79]).…”

Sulfanegen stimulates 3-mercaptopyruvate sulfurtransferase activity and ameliorates Alzheimer's disease pathology and oxidative stress in vivo

“…Supplementation of the H 2 S levels by systemic sulfurous water, sublimed sulfur, or inorganic sulfite salts have provided promising results in AD animal models, but clinical efficacy studies have thus far been inconclusive [ 13 , 14 ]. Instability of the H 2 S donors due to the ease of their oxidation and unpleasant odors of their formulations are factors that are partly responsible.…”