Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease
Alzheimer’s disease (AD) is characterized by the formation of intracellular aggregate composed of heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolysis cleavage of amyloid precursor protein (APP). Autophagy refers to the lysosomal-mediated de...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/1/5 |
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| author | Md. Ataur Rahman Md Saidur Rahman MD. Hasanur Rahman Mohammad Rasheduzzaman ANM Mamun-Or-Rashid Md Jamal Uddin Md Rezanur Rahman Hongik Hwang Myung-Geol Pang Hyewhon Rhim |
| author_facet | Md. Ataur Rahman Md Saidur Rahman MD. Hasanur Rahman Mohammad Rasheduzzaman ANM Mamun-Or-Rashid Md Jamal Uddin Md Rezanur Rahman Hongik Hwang Myung-Geol Pang Hyewhon Rhim |
| author_sort | Md. Ataur Rahman |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is characterized by the formation of intracellular aggregate composed of heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolysis cleavage of amyloid precursor protein (APP). Autophagy refers to the lysosomal-mediated degradation of cytoplasmic constituents, which plays a critical role in maintaining cellular homeostasis. Importantly, recent studies reported that dysregulation of autophagy is associated in the pathogenesis of AD, and therefore, autophagy modulation has gained attention as a promising approach to treat AD pathogenesis. In AD, both the maturation of autolysosomes and its retrograde transports have been obstructed, which causes the accumulation of autophagic vacuoles and eventually leads to degenerating and dystrophic neurites function. However, the mechanism of autophagy modulation in APP processing and its pathogenesis have not yet been fully elucidated in AD. In the early stage of AD, APP processing and Aβ accumulation-mediated autophagy facilitate the removal of toxic protein aggregates via mTOR-dependent and -independent pathways. In addition, a number of autophagy-related genes (Atg) and APP are thought to influence the development of AD, providing a bidirectional link between autophagy and AD pathology. In this review, we summarized the current observations related to autophagy regulation and APP processing in AD, focusing on their modulation associated with the AD progression. Moreover, we emphasizes the application of small molecules and natural compounds to modulate autophagy for the removal and clearance of APP and Aβ deposits in the pathological condition of AD. |
| first_indexed | 2024-03-10T13:49:05Z |
| format | Article |
| id | doaj.art-1b7c78504c9641b0b1e07ebdefc83e60 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T13:49:05Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-1b7c78504c9641b0b1e07ebdefc83e602023-11-21T02:20:52ZengMDPI AGBiomedicines2227-90592020-12-0191510.3390/biomedicines9010005Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s DiseaseMd. Ataur Rahman0Md Saidur Rahman1MD. Hasanur Rahman2Mohammad Rasheduzzaman3ANM Mamun-Or-Rashid4Md Jamal Uddin5Md Rezanur Rahman6Hongik Hwang7Myung-Geol Pang8Hyewhon Rhim9Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaDepartment of Animal Science & Technology and BET Research Institute, Chung-Ang University, Anseong 456-756, KoreaDepartment of Biotechnology and Genetic Engineering, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, BangladeshSchool of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, AustraliaAnti-Aging Medical Research Center and Glycation Stress Research Center, Graduate School of Life and Medical Sciences, Doshisha University, Kyoto 602-8566, JapanGraduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, KoreaDepartment of Biochemistry and Biotechnology, School of Biomedical Science, Khwaja Yunus Ali University, Sirajgonj 6751, BangladeshCenter for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaDepartment of Animal Science & Technology and BET Research Institute, Chung-Ang University, Anseong 456-756, KoreaCenter for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaAlzheimer’s disease (AD) is characterized by the formation of intracellular aggregate composed of heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolysis cleavage of amyloid precursor protein (APP). Autophagy refers to the lysosomal-mediated degradation of cytoplasmic constituents, which plays a critical role in maintaining cellular homeostasis. Importantly, recent studies reported that dysregulation of autophagy is associated in the pathogenesis of AD, and therefore, autophagy modulation has gained attention as a promising approach to treat AD pathogenesis. In AD, both the maturation of autolysosomes and its retrograde transports have been obstructed, which causes the accumulation of autophagic vacuoles and eventually leads to degenerating and dystrophic neurites function. However, the mechanism of autophagy modulation in APP processing and its pathogenesis have not yet been fully elucidated in AD. In the early stage of AD, APP processing and Aβ accumulation-mediated autophagy facilitate the removal of toxic protein aggregates via mTOR-dependent and -independent pathways. In addition, a number of autophagy-related genes (Atg) and APP are thought to influence the development of AD, providing a bidirectional link between autophagy and AD pathology. In this review, we summarized the current observations related to autophagy regulation and APP processing in AD, focusing on their modulation associated with the AD progression. Moreover, we emphasizes the application of small molecules and natural compounds to modulate autophagy for the removal and clearance of APP and Aβ deposits in the pathological condition of AD.https://www.mdpi.com/2227-9059/9/1/5autophagyamyloid precursor protein (APP)β-amyloid (Aβ)mTORAlzheimer’s disease (AD) |
| spellingShingle | Md. Ataur Rahman Md Saidur Rahman MD. Hasanur Rahman Mohammad Rasheduzzaman ANM Mamun-Or-Rashid Md Jamal Uddin Md Rezanur Rahman Hongik Hwang Myung-Geol Pang Hyewhon Rhim Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease Biomedicines autophagy amyloid precursor protein (APP) β-amyloid (Aβ) mTOR Alzheimer’s disease (AD) |
| title | Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease |
| title_full | Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease |
| title_fullStr | Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease |
| title_full_unstemmed | Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease |
| title_short | Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease |
| title_sort | modulatory effects of autophagy on app processing as a potential treatment target for alzheimer s disease |
| topic | autophagy amyloid precursor protein (APP) β-amyloid (Aβ) mTOR Alzheimer’s disease (AD) |
| url | https://www.mdpi.com/2227-9059/9/1/5 |
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