Endogenous and Synthetic Neurosteroids in the Treatment of Niemann–Pick Type C Disease

Abstract

Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science, 232, 1004-1007. 4. Harrison, N.L. and Simmonds, M.A. (1984) Modulation of GABA receptor complex by a steroid anesthetic. Brain Res., 323, 284-293. 5. Mensah-Nyagan, A.G., Beaujean, D., Luu-The, V., Pelletier, G., and Vaudry, H. (2001) Anatomical and biochemical evidence for the synthesis of unconjugated and sulfated neurosteroids in amphibians. Brain Res. Brain Res. Rev., 37, 13-24.

Assays of homeopathic remedies in rodent behavioural and psychopathological models

“…The stimulating effects of glycine and gelsemine suggest possible uses of glycinergic agents and gelsemine for stimulating these metabolic pathways involving neurosteroids, in disorders of the nervous system where they are reduced, and which are accompanied by symptoms of anxiety, social phobia, and potentially also psychiatric disorders 61,62 and encephalopathy. [63][64][65][66] Gelsemine was present in the mother tincture of the potencies used in our investigations at a concentration of 6.5 Â 10 À4 mol/l. Since each dilution step involves a 100 times decrease in concentration, the theoretical concentration of gelsemine in the 5CH, 7CH, 9CH and 30CH solutions was 6.5 Â 10 À14 , 6.5 Â 10 À18 , 6.5 Â 10 À22 and 6.5 Â 10 À64 mol/ l respectively.…”

Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer's disease compared to cognitively intact control subjects

“…For example, allopregnanolone is significantly decreased in Niemann-Pick type C mice, and one-time administration of this neurosteroid doubles lifespan and markedly delays neurological symptom onset [6–8]. The mechanisms by which allopregnanolone exerts these robust effects may include GABA A receptor modulation and activity at pregnane-X-receptors [8].…”

“…Allopregnanolone is a neurosteroid with a number of properties that may be relevant to the pathophysiology and treatment of Alzheimer’s disease (AD) and other neurodegenerative disorders, demonstrating pronounced neuroprotective actions in the setting of excitotoxicity [1, 2], traumatic brain injury (TBI) [3–5], and neurodegeneration [6–8]. It also increases myelination [9–11], enhances neurogenesis [12], decreases inflammation [11, 13, 14], and reduces apoptosis [15–17].…”

“…These include cholesterol dysregulation, neurofibrillary tangle formation, β-cleaved amyloid precursor protein accumulation, and myelin breakdown [28, 32–37]. Further, allopregnanolone administration delays neurological symptom onset and doubles lifespan in Niemann-Pick type C mice [6–8]. Also consistent with a role for allopregnanolone in disorders in which neurodegeneration is a salient characteristic, allopregnanolone and other neurosteroids are altered in AD.…”

The estrogenic retina: The potential contribution to healthy aging and age-related neurodegenerative diseases of the retina

“…[61] for review). Likewise oestradiol, allopregnanolone has been suggested to provide positive effects in diseases' models where neurosteoid synthesis is affected [58,128]. It is plausible to suspect that neuronal dysfunction affects the decision of neurosteroid biosynthetic pathways to promote neuroprotective or neurodegenerative agents in the context of their precise interaction with the neural network; external treatments with neurosteroids, including oestradiol, may validate or invalidate the final outcome of this decision.…”