New Insights into Alzheimer’s Disease: Novel Pathogenesis, Drug Target and Delivery
Alzheimer’s disease (AD), the most common type of dementia, is characterized by senile plaques composed of amyloid β protein (Aβ) and neurofilament tangles derived from the hyperphosphorylation of tau protein. However, the developed medicines targeting Aβ and tau have not obtained ideal clinical eff...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/4/1133 |
| _version_ | 1797603898262814720 |
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| author | Haishu Chen Jinan Xu Hanyuan Xu Tiancheng Luo Yihao Li Ke Jiang Yangping Shentu Zhiqian Tong |
| author_facet | Haishu Chen Jinan Xu Hanyuan Xu Tiancheng Luo Yihao Li Ke Jiang Yangping Shentu Zhiqian Tong |
| author_sort | Haishu Chen |
| collection | DOAJ |
| description | Alzheimer’s disease (AD), the most common type of dementia, is characterized by senile plaques composed of amyloid β protein (Aβ) and neurofilament tangles derived from the hyperphosphorylation of tau protein. However, the developed medicines targeting Aβ and tau have not obtained ideal clinical efficacy, which raises a challenge to the hypothesis that AD is Aβ cascade-induced. A critical problem of AD pathogenesis is which endogenous factor induces Aβ aggregation and tau phosphorylation. Recently, age-associated endogenous formaldehyde has been suggested to be a direct trigger for Aβ- and tau-related pathology. Another key issue is whether or not AD drugs are successfully delivered to the damaged neurons. Both the blood–brain barrier (BBB) and extracellular space (ECS) are the barriers for drug delivery. Unexpectedly, Aβ-related SP deposition in ECS slows down or stops interstitial fluid drainage in AD, which is the direct reason for drug delivery failure. Here, we propose a new pathogenesis and perspectives on the direction of AD drug development and drug delivery: (1) aging-related formaldehyde is a direct trigger for Aβ assembly and tau hyperphosphorylation, and the new target for AD therapy is formaldehyde; (2) nano-packaging and physical therapy may be the promising strategy for increasing BBB permeability and accelerating interstitial fluid drainage. |
| first_indexed | 2024-03-11T04:38:34Z |
| format | Article |
| id | doaj.art-bd19586bdf2c4cc980983afa6583f506 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T04:38:34Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-bd19586bdf2c4cc980983afa6583f5062023-11-17T20:53:11ZengMDPI AGPharmaceutics1999-49232023-04-01154113310.3390/pharmaceutics15041133New Insights into Alzheimer’s Disease: Novel Pathogenesis, Drug Target and DeliveryHaishu Chen0Jinan Xu1Hanyuan Xu2Tiancheng Luo3Yihao Li4Ke Jiang5Yangping Shentu6Zhiqian Tong7Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Institute of Aging, Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, School of Mental Health, Wenzhou Medical University, Wenzhou 325035, ChinaCixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Albert, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Albert, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Albert, Wenzhou Medical University, Wenzhou 325035, ChinaCixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Albert, Wenzhou Medical University, Wenzhou 325035, ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Institute of Aging, Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, School of Mental Health, Wenzhou Medical University, Wenzhou 325035, ChinaAlzheimer’s disease (AD), the most common type of dementia, is characterized by senile plaques composed of amyloid β protein (Aβ) and neurofilament tangles derived from the hyperphosphorylation of tau protein. However, the developed medicines targeting Aβ and tau have not obtained ideal clinical efficacy, which raises a challenge to the hypothesis that AD is Aβ cascade-induced. A critical problem of AD pathogenesis is which endogenous factor induces Aβ aggregation and tau phosphorylation. Recently, age-associated endogenous formaldehyde has been suggested to be a direct trigger for Aβ- and tau-related pathology. Another key issue is whether or not AD drugs are successfully delivered to the damaged neurons. Both the blood–brain barrier (BBB) and extracellular space (ECS) are the barriers for drug delivery. Unexpectedly, Aβ-related SP deposition in ECS slows down or stops interstitial fluid drainage in AD, which is the direct reason for drug delivery failure. Here, we propose a new pathogenesis and perspectives on the direction of AD drug development and drug delivery: (1) aging-related formaldehyde is a direct trigger for Aβ assembly and tau hyperphosphorylation, and the new target for AD therapy is formaldehyde; (2) nano-packaging and physical therapy may be the promising strategy for increasing BBB permeability and accelerating interstitial fluid drainage.https://www.mdpi.com/1999-4923/15/4/1133Alzheimer’s diseasedrug deliveryextracellular spaceblood–brain barrierformaldehydeinterstitial fluid |
| spellingShingle | Haishu Chen Jinan Xu Hanyuan Xu Tiancheng Luo Yihao Li Ke Jiang Yangping Shentu Zhiqian Tong New Insights into Alzheimer’s Disease: Novel Pathogenesis, Drug Target and Delivery Pharmaceutics Alzheimer’s disease drug delivery extracellular space blood–brain barrier formaldehyde interstitial fluid |
| title | New Insights into Alzheimer’s Disease: Novel Pathogenesis, Drug Target and Delivery |
| title_full | New Insights into Alzheimer’s Disease: Novel Pathogenesis, Drug Target and Delivery |
| title_fullStr | New Insights into Alzheimer’s Disease: Novel Pathogenesis, Drug Target and Delivery |
| title_full_unstemmed | New Insights into Alzheimer’s Disease: Novel Pathogenesis, Drug Target and Delivery |
| title_short | New Insights into Alzheimer’s Disease: Novel Pathogenesis, Drug Target and Delivery |
| title_sort | new insights into alzheimer s disease novel pathogenesis drug target and delivery |
| topic | Alzheimer’s disease drug delivery extracellular space blood–brain barrier formaldehyde interstitial fluid |
| url | https://www.mdpi.com/1999-4923/15/4/1133 |
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