Could protein phosphatase 2A and glycogen synthase kinase-3 beta be targeted by natural compounds to ameliorate Alzheimer’s pathologies?
Alzheimer’s disease (AD) is a progressive neurological disorder that impairs memory and cognitive abilities, primarily in the elderly. The burden of AD extends beyond patients, impacting families and caregivers due to the patients’ reliance on assistance for daily tasks. The main features of the pat...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024
|
| Online Access: | http://psasir.upm.edu.my/id/eprint/116408/ http://psasir.upm.edu.my/id/eprint/116408/1/116408.pdf |
| _version_ | 1848866997988753408 |
|---|---|
| author | Manoharan, Sushmitaa Dhevii Abdul Hamid, Hafizah Md Hashim, Nur Fariesha Cheema, Manraj Singh Musa Chiroma, Samaila Mustapha, Muzaimi Mehat, Muhammad Zulfadli |
| author_facet | Manoharan, Sushmitaa Dhevii Abdul Hamid, Hafizah Md Hashim, Nur Fariesha Cheema, Manraj Singh Musa Chiroma, Samaila Mustapha, Muzaimi Mehat, Muhammad Zulfadli |
| author_sort | Manoharan, Sushmitaa Dhevii |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Alzheimer’s disease (AD) is a progressive neurological disorder that impairs memory and cognitive abilities, primarily in the elderly. The burden of AD extends beyond patients, impacting families and caregivers due to the patients’ reliance on assistance for daily tasks. The main features of the pathogenesis of AD are beta-amyloid plaques and neurofibrillary tangles (NFTs), that strongly correlate with oxidative stress and inflammation. NFTs result from misfolded and hyperphosphorylated tau proteins. Various studies have focused on tau phosphorylation, indicating protein phosphatase 2A (PP2A) as the primary tau phosphatase and glycogen synthase kinase-3 beta (GSK-3β) as the leading tau kinase. Experimental evidence suggests that inhibition of PP2A and increased GSK-3β activity contribute to neuroinflammation, oxidative stress, and cognitive impairment. Hence, targeting PP2A and GSK-3β with pharmacological approaches shows promise in treating AD. The use of natural compounds in the drug development for AD have been extensively studied for their antioxidant, antiinflammatory, anti-cholinesterase, and neuroprotective properties, demonstrating therapeutic advantages in neurological diseases. Alongside the development of PP2A activator and GSK-3β inhibitor drugs, natural compounds are likely to have neuroprotective effects by increasing PP2A activity and decreasing GSK-3β levels. Therefore, based on the preclinical and clinical studies, the potential of PP2A and GSK-3β as therapeutic targets of natural compounds are highlighted in this review. |
| first_indexed | 2025-11-15T14:29:30Z |
| format | Article |
| id | upm-116408 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:29:30Z |
| publishDate | 2024 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1164082025-04-09T01:47:56Z http://psasir.upm.edu.my/id/eprint/116408/ Could protein phosphatase 2A and glycogen synthase kinase-3 beta be targeted by natural compounds to ameliorate Alzheimer’s pathologies? Manoharan, Sushmitaa Dhevii Abdul Hamid, Hafizah Md Hashim, Nur Fariesha Cheema, Manraj Singh Musa Chiroma, Samaila Mustapha, Muzaimi Mehat, Muhammad Zulfadli Alzheimer’s disease (AD) is a progressive neurological disorder that impairs memory and cognitive abilities, primarily in the elderly. The burden of AD extends beyond patients, impacting families and caregivers due to the patients’ reliance on assistance for daily tasks. The main features of the pathogenesis of AD are beta-amyloid plaques and neurofibrillary tangles (NFTs), that strongly correlate with oxidative stress and inflammation. NFTs result from misfolded and hyperphosphorylated tau proteins. Various studies have focused on tau phosphorylation, indicating protein phosphatase 2A (PP2A) as the primary tau phosphatase and glycogen synthase kinase-3 beta (GSK-3β) as the leading tau kinase. Experimental evidence suggests that inhibition of PP2A and increased GSK-3β activity contribute to neuroinflammation, oxidative stress, and cognitive impairment. Hence, targeting PP2A and GSK-3β with pharmacological approaches shows promise in treating AD. The use of natural compounds in the drug development for AD have been extensively studied for their antioxidant, antiinflammatory, anti-cholinesterase, and neuroprotective properties, demonstrating therapeutic advantages in neurological diseases. Alongside the development of PP2A activator and GSK-3β inhibitor drugs, natural compounds are likely to have neuroprotective effects by increasing PP2A activity and decreasing GSK-3β levels. Therefore, based on the preclinical and clinical studies, the potential of PP2A and GSK-3β as therapeutic targets of natural compounds are highlighted in this review. Elsevier 2024 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/116408/1/116408.pdf Manoharan, Sushmitaa Dhevii and Abdul Hamid, Hafizah and Md Hashim, Nur Fariesha and Cheema, Manraj Singh and Musa Chiroma, Samaila and Mustapha, Muzaimi and Mehat, Muhammad Zulfadli (2024) Could protein phosphatase 2A and glycogen synthase kinase-3 beta be targeted by natural compounds to ameliorate Alzheimer’s pathologies? Brain Research, 1829. art. no. 148793. pp. 1-16. ISSN 0006-8993; eISSN: 1872-6240 https://linkinghub.elsevier.com/retrieve/pii/S0006899324000477 10.1016/j.brainres.2024.148793 |
| spellingShingle | Manoharan, Sushmitaa Dhevii Abdul Hamid, Hafizah Md Hashim, Nur Fariesha Cheema, Manraj Singh Musa Chiroma, Samaila Mustapha, Muzaimi Mehat, Muhammad Zulfadli Could protein phosphatase 2A and glycogen synthase kinase-3 beta be targeted by natural compounds to ameliorate Alzheimer’s pathologies? |
| title | Could protein phosphatase 2A and glycogen synthase kinase-3 beta be targeted by natural compounds to ameliorate Alzheimer’s pathologies? |
| title_full | Could protein phosphatase 2A and glycogen synthase kinase-3 beta be targeted by natural compounds to ameliorate Alzheimer’s pathologies? |
| title_fullStr | Could protein phosphatase 2A and glycogen synthase kinase-3 beta be targeted by natural compounds to ameliorate Alzheimer’s pathologies? |
| title_full_unstemmed | Could protein phosphatase 2A and glycogen synthase kinase-3 beta be targeted by natural compounds to ameliorate Alzheimer’s pathologies? |
| title_short | Could protein phosphatase 2A and glycogen synthase kinase-3 beta be targeted by natural compounds to ameliorate Alzheimer’s pathologies? |
| title_sort | could protein phosphatase 2a and glycogen synthase kinase-3 beta be targeted by natural compounds to ameliorate alzheimer’s pathologies? |
| url | http://psasir.upm.edu.my/id/eprint/116408/ http://psasir.upm.edu.my/id/eprint/116408/ http://psasir.upm.edu.my/id/eprint/116408/ http://psasir.upm.edu.my/id/eprint/116408/1/116408.pdf |