Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s disease
Maintaining neuronal integrity and function requires precise mechanisms controlling organelle and protein quality. Alzheimer’s disease (AD) is also characterized by functional defects in the clearance and recycling of intracellular components. In fact, neuronal homeostasis involves autophagy, mitoph...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Compuscript Ltd
2022-01-01
|
| Series: | Acta Materia Medica |
| Subjects: | |
| Online Access: | https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2021-0002 |
| _version_ | 1797673960823848960 |
|---|---|
| author | Abdol-Hossein Rezaeian Wenyi Wei Hiroyuki Inuzuka |
| author_facet | Abdol-Hossein Rezaeian Wenyi Wei Hiroyuki Inuzuka |
| author_sort | Abdol-Hossein Rezaeian |
| collection | DOAJ |
| description | Maintaining neuronal integrity and function requires precise mechanisms controlling organelle and protein quality. Alzheimer’s disease (AD) is also characterized by functional defects in the clearance and recycling of intracellular components. In fact, neuronal homeostasis involves autophagy, mitophagy, apoptosis, and compromised activity in these cellular processes may cause pathological phenotypes of AD. Therefore, mitophagy is a critical mitochondrial quality-control system, and impaired mitophagy is a hallmark of AD. Myeloid cell leukemia 1 (MCL1), a member of the pro-survival B-cell lymphoma protein 2 (BCL2) family, is a mitochondrially targeted protein that contributes to maintaining mitochondrial integrity. Mcl1-knockout mice display peri-implantation lethality. Studies on conditional Mcl1-knockout mice have demonstrated that MCL1 plays a central role in neurogenesis and neuronal survival during brain development. Accumulating evidence indicates the critical role of MCL1 as a regulator of neuronal autophagy, mitophagy, and survival. In this review, we discuss the emerging neuroprotective function of MCL1 and how dysregulation of MCL1 signaling is involved in the pathogenesis of AD. Because members of the pro-survival BCL2 family proteins are promising targets of pharmacological intervention with BH3 mimetic drugs, we also discuss the promise of MCL1-targeting therapy in AD. |
| first_indexed | 2024-03-11T21:52:01Z |
| format | Article |
| id | doaj.art-fbb0563d747c4fb6a58d248bc090a8f7 |
| institution | Directory Open Access Journal |
| issn | 2737-7946 |
| language | English |
| last_indexed | 2024-03-11T21:52:01Z |
| publishDate | 2022-01-01 |
| publisher | Compuscript Ltd |
| record_format | Article |
| series | Acta Materia Medica |
| spelling | doaj.art-fbb0563d747c4fb6a58d248bc090a8f72023-09-26T08:59:34ZengCompuscript LtdActa Materia Medica2737-79462022-01-0111425510.15212/AMM-2021-0002Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s diseaseAbdol-Hossein Rezaeian0Wenyi Wei1Hiroyuki Inuzuka2Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesMaintaining neuronal integrity and function requires precise mechanisms controlling organelle and protein quality. Alzheimer’s disease (AD) is also characterized by functional defects in the clearance and recycling of intracellular components. In fact, neuronal homeostasis involves autophagy, mitophagy, apoptosis, and compromised activity in these cellular processes may cause pathological phenotypes of AD. Therefore, mitophagy is a critical mitochondrial quality-control system, and impaired mitophagy is a hallmark of AD. Myeloid cell leukemia 1 (MCL1), a member of the pro-survival B-cell lymphoma protein 2 (BCL2) family, is a mitochondrially targeted protein that contributes to maintaining mitochondrial integrity. Mcl1-knockout mice display peri-implantation lethality. Studies on conditional Mcl1-knockout mice have demonstrated that MCL1 plays a central role in neurogenesis and neuronal survival during brain development. Accumulating evidence indicates the critical role of MCL1 as a regulator of neuronal autophagy, mitophagy, and survival. In this review, we discuss the emerging neuroprotective function of MCL1 and how dysregulation of MCL1 signaling is involved in the pathogenesis of AD. Because members of the pro-survival BCL2 family proteins are promising targets of pharmacological intervention with BH3 mimetic drugs, we also discuss the promise of MCL1-targeting therapy in AD.https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2021-0002alzheimer’s diseasemitochondriaautophagymitophagyapoptosismcl1bh3 mimetics |
| spellingShingle | Abdol-Hossein Rezaeian Wenyi Wei Hiroyuki Inuzuka Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s disease Acta Materia Medica alzheimer’s disease mitochondria autophagy mitophagy apoptosis mcl1 bh3 mimetics |
| title | Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s disease |
| title_full | Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s disease |
| title_fullStr | Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s disease |
| title_full_unstemmed | Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s disease |
| title_short | Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s disease |
| title_sort | regulation of neuronal autophagy and cell survival by mcl1 in alzheimer s disease |
| topic | alzheimer’s disease mitochondria autophagy mitophagy apoptosis mcl1 bh3 mimetics |
| url | https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2021-0002 |
| work_keys_str_mv | AT abdolhosseinrezaeian regulationofneuronalautophagyandcellsurvivalbymcl1inalzheimersdisease AT wenyiwei regulationofneuronalautophagyandcellsurvivalbymcl1inalzheimersdisease AT hiroyukiinuzuka regulationofneuronalautophagyandcellsurvivalbymcl1inalzheimersdisease |