PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy
As a primary cause of dementia and death in older people, Alzheimer’s disease (AD) has become a common problem and challenge worldwide. Abnormal accumulation of tau proteins in the brain is a hallmark pathology of AD and is closely related to the clinical progression and severity of cognitive defici...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-01-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.736267/full |
| _version_ | 1811190560497598464 |
|---|---|
| author | Xing Jun Jiang Yan Qing Wu Rong Ma Yan Min Chang Lu Lu Li Jia Hui Zhu Gong Ping Liu Gong Ping Liu Gang Li |
| author_facet | Xing Jun Jiang Yan Qing Wu Rong Ma Yan Min Chang Lu Lu Li Jia Hui Zhu Gong Ping Liu Gong Ping Liu Gang Li |
| author_sort | Xing Jun Jiang |
| collection | DOAJ |
| description | As a primary cause of dementia and death in older people, Alzheimer’s disease (AD) has become a common problem and challenge worldwide. Abnormal accumulation of tau proteins in the brain is a hallmark pathology of AD and is closely related to the clinical progression and severity of cognitive deficits. Here, we found that overexpression of phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) effectively promoted the degradation of tau, thereby rescuing neuron loss, synaptic damage, and cognitive impairments in a mouse model of tauopathy with AAV-full-length human Tau (hTau) injected into the hippocampal CA1 area (hTau mice). Overexpression of PINK1 activated autophagy, and chloroquine but not MG132 reversed the PINK1-induced decrease in human Tau levels and cognitive improvement in hTau mice. Furthermore, PINK1 also ameliorated mitochondrial dysfunction induced by hTau. Taken together, our data revealed that PINK1 overexpression promoted degradation of abnormal accumulated tau via the autophagy–lysosome pathway, indicating that PINK1 may be a potential target for AD treatment. |
| first_indexed | 2024-04-11T14:53:05Z |
| format | Article |
| id | doaj.art-b4760cfe6ef74b0193dc07b49564b0d6 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T14:53:05Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-b4760cfe6ef74b0193dc07b49564b0d62022-12-22T04:17:22ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-01910.3389/fcell.2021.736267736267PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of TauopathyXing Jun Jiang0Yan Qing Wu1Rong Ma2Yan Min Chang3Lu Lu Li4Jia Hui Zhu5Gong Ping Liu6Gong Ping Liu7Gang Li8Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCo-Innovation Center of Neuroregeneration, Nantong University, Nantong, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaAs a primary cause of dementia and death in older people, Alzheimer’s disease (AD) has become a common problem and challenge worldwide. Abnormal accumulation of tau proteins in the brain is a hallmark pathology of AD and is closely related to the clinical progression and severity of cognitive deficits. Here, we found that overexpression of phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) effectively promoted the degradation of tau, thereby rescuing neuron loss, synaptic damage, and cognitive impairments in a mouse model of tauopathy with AAV-full-length human Tau (hTau) injected into the hippocampal CA1 area (hTau mice). Overexpression of PINK1 activated autophagy, and chloroquine but not MG132 reversed the PINK1-induced decrease in human Tau levels and cognitive improvement in hTau mice. Furthermore, PINK1 also ameliorated mitochondrial dysfunction induced by hTau. Taken together, our data revealed that PINK1 overexpression promoted degradation of abnormal accumulated tau via the autophagy–lysosome pathway, indicating that PINK1 may be a potential target for AD treatment.https://www.frontiersin.org/articles/10.3389/fcell.2021.736267/fulltauPINK1autophagymemoryAlzheimer’s disease |
| spellingShingle | Xing Jun Jiang Yan Qing Wu Rong Ma Yan Min Chang Lu Lu Li Jia Hui Zhu Gong Ping Liu Gong Ping Liu Gang Li PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy Frontiers in Cell and Developmental Biology tau PINK1 autophagy memory Alzheimer’s disease |
| title | PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy |
| title_full | PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy |
| title_fullStr | PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy |
| title_full_unstemmed | PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy |
| title_short | PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy |
| title_sort | pink1 alleviates cognitive impairments via attenuating pathological tau aggregation in a mouse model of tauopathy |
| topic | tau PINK1 autophagy memory Alzheimer’s disease |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.736267/full |
| work_keys_str_mv | AT xingjunjiang pink1alleviatescognitiveimpairmentsviaattenuatingpathologicaltauaggregationinamousemodeloftauopathy AT yanqingwu pink1alleviatescognitiveimpairmentsviaattenuatingpathologicaltauaggregationinamousemodeloftauopathy AT rongma pink1alleviatescognitiveimpairmentsviaattenuatingpathologicaltauaggregationinamousemodeloftauopathy AT yanminchang pink1alleviatescognitiveimpairmentsviaattenuatingpathologicaltauaggregationinamousemodeloftauopathy AT lululi pink1alleviatescognitiveimpairmentsviaattenuatingpathologicaltauaggregationinamousemodeloftauopathy AT jiahuizhu pink1alleviatescognitiveimpairmentsviaattenuatingpathologicaltauaggregationinamousemodeloftauopathy AT gongpingliu pink1alleviatescognitiveimpairmentsviaattenuatingpathologicaltauaggregationinamousemodeloftauopathy AT gongpingliu pink1alleviatescognitiveimpairmentsviaattenuatingpathologicaltauaggregationinamousemodeloftauopathy AT gangli pink1alleviatescognitiveimpairmentsviaattenuatingpathologicaltauaggregationinamousemodeloftauopathy |