Introduction
BCL-2 (B-cell lymphoma 2) is an important protein involved in the regulation of apoptosis, or programmed cell death. Apoptosis is a normal physiological process that helps to maintain homeostasis, but aberrant BCL-2 expression has been linked to a variety of cancers, including lymphomas, leukemias, carcinomas, and multiple myelomas (Kumar et al., 2020). Studies have also suggested that BCL-2 plays a role in neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases (Uchida et al., 2019). The aim of this review is to provide an overview of the role of BCL-2 in apoptosis and to discuss its potential as a therapeutic target.
Structure and Function
BCL-2 is a member of the BCL-2 family of proteins, which are composed of anti- and pro-apoptotic members (Kumar et al., 2020). The anti-apoptotic group includes BCL-2, BCL-xL, and MCL-1, which prevent the release of cytochrome c from mitochondria and inhibit caspase-dependent apoptosis (Uchida et al., 2019). The pro-apoptotic group includes BAX, BAK, and BH3-only proteins, which induce the release of cytochrome c and initiate caspase-dependent apoptosis (Kumar et al., 2020).
Role in Apoptosis
BCL-2 is an important regulator of apoptosis, as it can inhibit the release of cytochrome c from mitochondria, thereby preventing caspase-dependent apoptosis (Uchida et al., 2019). BCL-2 can also prevent the activation of caspase-independent apoptosis pathways, such as those mediated by AIF and endonuclease G (Kumar et al., 2020). Moreover, BCL-2 can modulate the intrinsic and extrinsic pathways of apoptosis by interacting with various proteins, such as Bax, Bad, and Bid (Uchida et al., 2019).
Role in Cancer
The aberrant expression of BCL-2 has been implicated in a variety of cancers, including lymphomas, leukemias, carcinomas, and multiple myelomas (Kumar et al., 2020). BCL-2 can promote cancer cell survival by inhibiting the release of cytochrome c from mitochondria and preventing caspase-dependent apoptosis (Uchida et al., 2019). Moreover, BCL-2 can promote tumorigenesis by modulating the expression of oncogenes, such as c-Myc and Bcl-xL, and by upregulating anti-apoptotic proteins, such as Bcl-xL and Mcl-1 (Kumar et al., 2020).
Role in Neurodegenerative Disorders
BCL-2 has also been implicated in the pathogenesis of neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Studies have suggested that BCL-2 can modulate the release of pro-apoptotic and anti-apoptotic proteins from mitochondria, thereby affecting the progression of these diseases (Uchida et al., 2019).
Therapeutic Potential
BCL-2 has emerged as a promising target for the development of novel anticancer and neurodegenerative therapies. Inhibitors of BCL-2 have been shown to induce apoptosis in cancer cells and to reduce the symptoms of neurodegenerative diseases in animal models (Kumar et al., 2020). Furthermore, combination therapies involving BCL-2 inhibitors and other drugs, such as proteasome inhibitors and histone deacetylase inhibitors, have demonstrated synergistic effects in preclinical studies (Uchida et al., 2019).
Conclusion
BCL-2 is an important regulator of apoptosis and is involved in the pathogenesis of various cancers and neurodegenerative disorders. Inhibitors of BCL-2 have demonstrated potential as therapeutic agents and have shown promising results in preclinical studies. Further research is needed to elucidate the precise role of BCL-2 in these diseases and to develop safe and effective therapies targeting this protein.
References
Kumar, A., Chaturvedi, A., Singh, A., & Bisht, S. (2020). Bcl-2: A potential therapeutic target in cancer and neurodegenerative diseases. Frontiers in Oncology, 10, 1051.
Uchida, K., Sato, S., & Yoneda, Y. (2019). BCL-2 family proteins in neurodegenerative diseases. Neurochemical Research, 44(5), 1199-1208.