TY - JOUR
T1 - The role of Bcl-2 proteins in modulating neuronal Ca2+ signaling in health and in Alzheimer's disease
AU - Callens, Manon
AU - Kraskovskaya, Nina
AU - Derevtsova, Kristina
AU - Annaert, Wim
AU - Bultynck, Geert
AU - Bezprozvanny, Ilya
AU - Vervliet, Tim
N1 - Funding Information:
Research in the authors' laboratories was supported by research grants of the Research Foundation - Flanders (FWO) (grants G.0634.13N, G.0C91.14N, G.0A34.16N and G090118N to GB and grant G0E7520N to GB and IB; S006617N, G078117N, G056017N, G0C4220N to WA), the Research Council - KU Leuven (OT14/101, C14/19/101 and AKUL/19/34 to GB; C16/15/073 to WA), VIB (to WA), Central European Leuven Strategic Alliance (CELSA/18/040 to GB), Stichting Alzheimer Onderzoek (SAO IP3 RECEPTOR to GB; SAO-FRA #2020-0030 to WA), Eye Hope Foundation/Koning Boudewijnstichting (2020-J1160630-214966 to GB), National Institutes of Health grant R01AG055577 (IB) and Russian Science Foundation grant 20-45-01004 (IB). IB is a holder of the Carl J. and Hortense M. Thomsen Chair in Alzheimer's Disease Research.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/5
Y1 - 2021/5
N2 - 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 Ca2+ 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 Ca2+ signaling plays an important role in the pathogenesis of AD, and we propose that dysregulation of the Bcl-2-Ca2+ 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.
AB - 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 Ca2+ 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 Ca2+ signaling plays an important role in the pathogenesis of AD, and we propose that dysregulation of the Bcl-2-Ca2+ 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.
KW - Alzheimer's disease
KW - Apoptosis
KW - Bcl-2
KW - Calcium
KW - Mitochondria
KW - Neurons
UR - http://www.scopus.com/inward/record.url?scp=85102262119&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102262119&partnerID=8YFLogxK
U2 - 10.1016/j.bbamcr.2021.118997
DO - 10.1016/j.bbamcr.2021.118997
M3 - Review article
C2 - 33711363
AN - SCOPUS:85102262119
VL - 1868
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
SN - 0167-4889
IS - 6
M1 - 118997
ER -