Autophagy Modulation as a Treatment of Amyloid Diseases
Amyloids are fibrous proteins aggregated into toxic forms that are implicated in several chronic disorders. More than 30 diseases show deposition of fibrous amyloid proteins associated with cell loss and degeneration in the affected tissues. Evidence demonstrates that amyloid diseases result from pr...
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| Format: | Article |
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MDPI AG
2019-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/18/3372 |
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| author | Zoe Mputhia Eugene Hone Timir Tripathi Tim Sargeant Ralph Martins Prashant Bharadwaj |
| author_facet | Zoe Mputhia Eugene Hone Timir Tripathi Tim Sargeant Ralph Martins Prashant Bharadwaj |
| author_sort | Zoe Mputhia |
| collection | DOAJ |
| description | Amyloids are fibrous proteins aggregated into toxic forms that are implicated in several chronic disorders. More than 30 diseases show deposition of fibrous amyloid proteins associated with cell loss and degeneration in the affected tissues. Evidence demonstrates that amyloid diseases result from protein aggregation or impaired amyloid clearance, but the connection between amyloid accumulation and tissue degeneration is not clear. Common examples of amyloid diseases are Alzheimer’s disease (AD), Parkinson’s disease (PD) and tauopathies, which are the most common forms of neurodegenerative diseases, as well as polyglutamine disorders and certain peripheral metabolic diseases. In these diseases, increased accumulation of toxic amyloid proteins is suspected to be one of the main causative factors in the disease pathogenesis. It is therefore important to more clearly understand how these toxic amyloid proteins accumulate as this will aide in the development of more effective preventive and therapeutic strategies. Protein homeostasis, or proteostasis, is maintained by multiple cellular pathways—including protein synthesis, quality control, and clearance—which are collectively responsible for preventing protein misfolding or aggregation. Modulating protein degradation is a very complex but attractive treatment strategy used to remove amyloid and improve cell survival. This review will focus on autophagy, an important clearance pathway of amyloid proteins, and strategies for using it as a potential therapeutic target for amyloid diseases. The physiological role of autophagy in cells, pathways for its modulation, its connection with apoptosis, cell models and caveats in developing autophagy as a treatment and as a biomarker is discussed. |
| first_indexed | 2024-12-20T19:04:48Z |
| format | Article |
| id | doaj.art-a979a5eb492b4214b6f1cfc322f9568c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-20T19:04:48Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a979a5eb492b4214b6f1cfc322f9568c2022-12-21T19:29:18ZengMDPI AGMolecules1420-30492019-09-012418337210.3390/molecules24183372molecules24183372Autophagy Modulation as a Treatment of Amyloid DiseasesZoe Mputhia0Eugene Hone1Timir Tripathi2Tim Sargeant3Ralph Martins4Prashant Bharadwaj5Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Nedlands, WA 6009, AustraliaCentre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Nedlands, WA 6009, AustraliaDepartment of Biochemistry, North-Eastern Hill University, Meghalaya 793022, IndiaHopwood Centre for Neurobiology, SAHMRI, Adelaide, SA 5000, AustraliaCentre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Nedlands, WA 6009, AustraliaCentre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Nedlands, WA 6009, AustraliaAmyloids are fibrous proteins aggregated into toxic forms that are implicated in several chronic disorders. More than 30 diseases show deposition of fibrous amyloid proteins associated with cell loss and degeneration in the affected tissues. Evidence demonstrates that amyloid diseases result from protein aggregation or impaired amyloid clearance, but the connection between amyloid accumulation and tissue degeneration is not clear. Common examples of amyloid diseases are Alzheimer’s disease (AD), Parkinson’s disease (PD) and tauopathies, which are the most common forms of neurodegenerative diseases, as well as polyglutamine disorders and certain peripheral metabolic diseases. In these diseases, increased accumulation of toxic amyloid proteins is suspected to be one of the main causative factors in the disease pathogenesis. It is therefore important to more clearly understand how these toxic amyloid proteins accumulate as this will aide in the development of more effective preventive and therapeutic strategies. Protein homeostasis, or proteostasis, is maintained by multiple cellular pathways—including protein synthesis, quality control, and clearance—which are collectively responsible for preventing protein misfolding or aggregation. Modulating protein degradation is a very complex but attractive treatment strategy used to remove amyloid and improve cell survival. This review will focus on autophagy, an important clearance pathway of amyloid proteins, and strategies for using it as a potential therapeutic target for amyloid diseases. The physiological role of autophagy in cells, pathways for its modulation, its connection with apoptosis, cell models and caveats in developing autophagy as a treatment and as a biomarker is discussed.https://www.mdpi.com/1420-3049/24/18/3372amyloidautophagyclearancetoxicitylysosomeAlzheimer’s diseaseParkinson’s diseasepolyglutamineTau proteinbeta amyloidα-synucleinHuntington’s disease |
| spellingShingle | Zoe Mputhia Eugene Hone Timir Tripathi Tim Sargeant Ralph Martins Prashant Bharadwaj Autophagy Modulation as a Treatment of Amyloid Diseases Molecules amyloid autophagy clearance toxicity lysosome Alzheimer’s disease Parkinson’s disease polyglutamine Tau protein beta amyloid α-synuclein Huntington’s disease |
| title | Autophagy Modulation as a Treatment of Amyloid Diseases |
| title_full | Autophagy Modulation as a Treatment of Amyloid Diseases |
| title_fullStr | Autophagy Modulation as a Treatment of Amyloid Diseases |
| title_full_unstemmed | Autophagy Modulation as a Treatment of Amyloid Diseases |
| title_short | Autophagy Modulation as a Treatment of Amyloid Diseases |
| title_sort | autophagy modulation as a treatment of amyloid diseases |
| topic | amyloid autophagy clearance toxicity lysosome Alzheimer’s disease Parkinson’s disease polyglutamine Tau protein beta amyloid α-synuclein Huntington’s disease |
| url | https://www.mdpi.com/1420-3049/24/18/3372 |
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