Precursors of coenzyme A-panthenol and pantethine-in the mechanisms of neuroprotection

• Autorzy: Moiseenok A.G.
• Języki publikacji: EN

Abstrakty

EN

The results of clinicalstudies on coenzymeA(CoA) biosynthetic precursors carried out over 30 years revealed and confirmed neuroprotective properties of D-panthenol (PL) and D-pantethine (PT). The efficiency of all these drug formulations was demonstrated both in the alcohol withdrawal syndrome and delirium tremens, during involution psychosis, for prevention and treatment of the brain post-ischemic syndrome and surgery of arterial aneurisms. Parallel preclinical studies revealed high efficiency of the CoA precursors in focal brain ischemia, aluminum neurotoxicosis, bacterial lipopolysaccharide and cholinotoxin exposures and modulation of the effects of nootropic pharmacologic agents eliminating neurologic deficiency. The participation of CoA-dependent mechanisms on administration of amyloid P-peptide and m-anticholinergic drugs was shown. The ability of CoA precursors to prevent development of oxidative stress (OS), endogenous intoxication and immobilization stress was determined. A protective effect of PT was found in vagotomy. Comparative pharmacokinetic studies on bioavailability of PT and PL in the albino rat CNS showed the presence of differencesin the processes of “uptake”, transport, deposition and biotransformation in individual neurostructures with preferential accumulation of 4’- phosphopantothenic acid (PPA). The [ 3 H]J-PT perfusion of hippocampus sections was also accompanied by accumulation of PPA as a result of possible hydrolysis by phospho-PTpantethinase (Vanin-1).The role of PPAis unclear, but it can be related to the balance of the Fe2+/Fe3+ and cysteine/cystine redox pairs. It has been established that the neuroprotective effect of the CoA precursors is realized through stabilization of neuromembranes, as well as the glutathione and acetylcholine systems in the CNS and is possibly mediated through the cellular redox potential and redox signaling by OS products and the processes of post-translation protein modification (S-glutathionylation).

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S28

Twórcy

autor

Moiseenok A.G.

• Institute of Biochemistry of Biological Active Compounds, NAS of Belarus, Grodno, Belarus