The role of Bcl-2 proteins in modulating neuronal Ca signaling in health and in Alzheimer's disease.

Manon Callens, Nina Kraskovskaya, Kristina Derevtsova, Wim Annaert, Geert Bultynck, Ilya Bezprozvanny, Tim Vervliet

Journal: Biochimica et biophysica acta. Molecular cell research 2021;1868(6):118997

PMID: 33711363

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Abstract

The family of B-cell lymphoma-2 (Bcl-2) proteins exerts key functions in cellular health. Bcl-2 primarily acts in mitochondria where it controls the initiation of apoptosis. However, during the last decades, it has become clear that this family of proteins is also involved in controlling intracellular Ca signaling, a critical process for the function of most cell types, including neurons. Several anti- and pro-apoptotic Bcl-2 family members are expressed in neurons and impact neuronal function. Importantly, expression levels of neuronal Bcl-2 proteins are affected by age. In this review, we focus on the emerging roles of Bcl-2 proteins in neuronal cells. Specifically, we discuss how their dysregulation contributes to the onset, development, and progression of neurodegeneration in the context of Alzheimer's disease (AD). Aberrant Ca signaling plays an important role in the pathogenesis of AD, and we propose that dysregulation of the Bcl-2-Ca signaling axis may contribute to the progression of AD and that herein, Bcl-2 may constitute a potential therapeutic target for the treatment of AD.

Address: KU Leuven, Laboratory of Molecular & Cellular Signaling, Department of Cellular & Molecular Medicine, Campus Gasthuisberg O/N-I bus 802, Herestraat 49, BE-3000 Leuven, Belgium.; Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg State Polytechnic University, Saint Petersburg, Russia.; Laboratory for Membrane Trafficking, VIB Center for Brain and Disease Research & KU Leuven, Department of Neurosciences, Gasthuisberg, O&N5, Rm 7.357, B-3000 Leuven, Belgium.; KU Leuven, Laboratory of Molecular & Cellular Signaling, Department of Cellular & Molecular Medicine, Campus Gasthuisberg O/N-I bus 802, Herestraat 49, BE-3000 Leuven, Belgium. Electronic address: [email protected].; Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg State Polytechnic University, Saint Petersburg, Russia; Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, TX, United States. Electronic address: [email protected].

DOI: 10.1016/j.bbamcr.2021.118997

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Full Text Sources:

Medical:

https://medlineplus.gov/alzheimersdisease.html

Other Literature Sources:

https://scite.ai/reports/33711363

Miscellaneous:

https://assays.cancer.gov/CPTAC-177

MeSH Terms: Age Factors, Alzheimer Disease, Calcium Signaling, Disease Progression, Gene Expression Regulation, Humans, Neurons, Proto-Oncogene Proteins c-bcl-2