SERCA pump as a novel therapeutic target for treating neurodegenerative disorders.

Autor: Dahl R; Neurodon Corporation, 9800 Connecticut Drive, Crown Point, IN, 46307, USA. Electronic address: rdahl@neurodon.net., Bezprozvanny I; Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg Polytechnical University, St. Petersburg, Russia. Electronic address: mnlabspb@gmail.com.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Nov 19; Vol. 734, pp. 150748. Date of Electronic Publication: 2024 Sep 26.
DOI: 10.1016/j.bbrc.2024.150748
Abstrakt: The neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Spinocerebellar ataxias (SCAs), present an enormous medical, social, financial and scientific problem. Despite intense research into the causes of these disorders, only marginal progress has been made in the clinic and no cures exist for any of them. Most of the scientific effort has been focused on identification of the major causes of these diseases and on developing ways to target them, such as targeting amyloid accumulation for AD or targeting expression of mutant Huntingtin for HD. Calcium (Ca 2+ ) signaling has long been proposed to play an important role in the pathogenesis of neurodegenerative disorders, but blockers of Ca 2+ channels and Ca 2+ signaling proteins have not been translated to clinic primarily due to side effects related to the important roles of target molecules for these compounds at the peripheral tissues. In this review article, we would like to discuss an idea that recently identified positive allosteric modulators (PAMs) of the sarco-endoplasmic reticulum calcium (SERCA) pump may provide a promising approach to develop therapeutic compounds for treatment of these disorders. This hypothesis is supported by the preclinical data obtained with animal models of AD and PD. The first critical test of this idea will be an imminent phase I study that will offer an opportunity to evaluate potential side effects of this class of compounds in humans.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R.D. is an inventor of the patents US11,730,729, US11,821,626, US10,772,881, and WO2022/020261 “Quinolines that modulate SERCA and their use for treating disease” that describe all of the compounds disclosed herein and are assigned to Neurodon Corporation. Part of the cost of this research was paid for by Neurodon. R.D. is an employee of Neurodon. I.B. is a member of Neurodon SAB. R.D. and I.B. hold Neurodon stock or stock options
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: