Interplay Between the Autophagy-Lysosomal Pathway and the Ubiquitin-Proteasome System: A Target for Therapeutic Development in Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common cause of age-related dementia leading to severe irreversible cognitive decline and massive neurodegeneration. While therapeutic approaches for managing symptoms are available, AD currently has no cure. AD associates with a progressive decline of the two ma...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-05-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2018.00126/full |
| _version_ | 1798045730025242624 |
|---|---|
| author | Hianara A. Bustamante Hianara A. Bustamante Alexis E. González Alexis E. González Cristobal Cerda-Troncoso Ronan Shaughnessy Ronan Shaughnessy Carola Otth Carola Otth Andrea Soza Andrea Soza Patricia V. Burgos Patricia V. Burgos Patricia V. Burgos |
| author_facet | Hianara A. Bustamante Hianara A. Bustamante Alexis E. González Alexis E. González Cristobal Cerda-Troncoso Ronan Shaughnessy Ronan Shaughnessy Carola Otth Carola Otth Andrea Soza Andrea Soza Patricia V. Burgos Patricia V. Burgos Patricia V. Burgos |
| author_sort | Hianara A. Bustamante |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most common cause of age-related dementia leading to severe irreversible cognitive decline and massive neurodegeneration. While therapeutic approaches for managing symptoms are available, AD currently has no cure. AD associates with a progressive decline of the two major catabolic pathways of eukaryotic cells—the autophagy-lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS)—that contributes to the accumulation of harmful molecules implicated in synaptic plasticity and long-term memory impairment. One protein recently highlighted as the earliest initiator of these disturbances is the amyloid precursor protein (APP) intracellular C-terminal membrane fragment β (CTFβ), a key toxic agent with deleterious effects on neuronal function that has become an important pathogenic factor for AD and a potential biomarker for AD patients. This review focuses on the involvement of regulatory molecules and specific post-translational modifications (PTMs) that operate in the UPS and ALP to control a single proteostasis network to achieve protein balance. We discuss how these aspects can contribute to the development of novel strategies to strengthen the balance of key pathogenic proteins associated with AD. |
| first_indexed | 2024-04-11T23:25:53Z |
| format | Article |
| id | doaj.art-d9aff8b30736479b82f14b7327cfa287 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-11T23:25:53Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-d9aff8b30736479b82f14b7327cfa2872022-12-22T03:57:19ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-05-011210.3389/fncel.2018.00126357128Interplay Between the Autophagy-Lysosomal Pathway and the Ubiquitin-Proteasome System: A Target for Therapeutic Development in Alzheimer’s DiseaseHianara A. Bustamante0Hianara A. Bustamante1Alexis E. González2Alexis E. González3Cristobal Cerda-Troncoso4Ronan Shaughnessy5Ronan Shaughnessy6Carola Otth7Carola Otth8Andrea Soza9Andrea Soza10Patricia V. Burgos11Patricia V. Burgos12Patricia V. Burgos13Institute of Physiology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, ChileCenter for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, ChileInstitute of Physiology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, ChileFundación Ciencia y Vida, Santiago, ChileCentro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, ChileCentro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, ChileCenter for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileCenter for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, ChileInstitute of Clinical Microbiology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, ChileCentro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, ChileCenter for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileInstitute of Physiology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, ChileCentro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, ChileCenter for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileAlzheimer’s disease (AD) is the most common cause of age-related dementia leading to severe irreversible cognitive decline and massive neurodegeneration. While therapeutic approaches for managing symptoms are available, AD currently has no cure. AD associates with a progressive decline of the two major catabolic pathways of eukaryotic cells—the autophagy-lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS)—that contributes to the accumulation of harmful molecules implicated in synaptic plasticity and long-term memory impairment. One protein recently highlighted as the earliest initiator of these disturbances is the amyloid precursor protein (APP) intracellular C-terminal membrane fragment β (CTFβ), a key toxic agent with deleterious effects on neuronal function that has become an important pathogenic factor for AD and a potential biomarker for AD patients. This review focuses on the involvement of regulatory molecules and specific post-translational modifications (PTMs) that operate in the UPS and ALP to control a single proteostasis network to achieve protein balance. We discuss how these aspects can contribute to the development of novel strategies to strengthen the balance of key pathogenic proteins associated with AD.http://journal.frontiersin.org/article/10.3389/fncel.2018.00126/fullAlzheimer’s diseaseubiquitinproteasomeautophagylysosomesHSV-1 |
| spellingShingle | Hianara A. Bustamante Hianara A. Bustamante Alexis E. González Alexis E. González Cristobal Cerda-Troncoso Ronan Shaughnessy Ronan Shaughnessy Carola Otth Carola Otth Andrea Soza Andrea Soza Patricia V. Burgos Patricia V. Burgos Patricia V. Burgos Interplay Between the Autophagy-Lysosomal Pathway and the Ubiquitin-Proteasome System: A Target for Therapeutic Development in Alzheimer’s Disease Frontiers in Cellular Neuroscience Alzheimer’s disease ubiquitin proteasome autophagy lysosomes HSV-1 |
| title | Interplay Between the Autophagy-Lysosomal Pathway and the Ubiquitin-Proteasome System: A Target for Therapeutic Development in Alzheimer’s Disease |
| title_full | Interplay Between the Autophagy-Lysosomal Pathway and the Ubiquitin-Proteasome System: A Target for Therapeutic Development in Alzheimer’s Disease |
| title_fullStr | Interplay Between the Autophagy-Lysosomal Pathway and the Ubiquitin-Proteasome System: A Target for Therapeutic Development in Alzheimer’s Disease |
| title_full_unstemmed | Interplay Between the Autophagy-Lysosomal Pathway and the Ubiquitin-Proteasome System: A Target for Therapeutic Development in Alzheimer’s Disease |
| title_short | Interplay Between the Autophagy-Lysosomal Pathway and the Ubiquitin-Proteasome System: A Target for Therapeutic Development in Alzheimer’s Disease |
| title_sort | interplay between the autophagy lysosomal pathway and the ubiquitin proteasome system a target for therapeutic development in alzheimer s disease |
| topic | Alzheimer’s disease ubiquitin proteasome autophagy lysosomes HSV-1 |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2018.00126/full |
| work_keys_str_mv | AT hianaraabustamante interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT hianaraabustamante interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT alexisegonzalez interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT alexisegonzalez interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT cristobalcerdatroncoso interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT ronanshaughnessy interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT ronanshaughnessy interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT carolaotth interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT carolaotth interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT andreasoza interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT andreasoza interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT patriciavburgos interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT patriciavburgos interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease AT patriciavburgos interplaybetweentheautophagylysosomalpathwayandtheubiquitinproteasomesystematargetfortherapeuticdevelopmentinalzheimersdisease |