Mechanistic and therapeutic role of Drp1 in the pathogenesis of Alzheimer's disease.

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Title: Mechanistic and therapeutic role of Drp1 in the pathogenesis of Alzheimer's disease.
Authors: Bera, Arpita (AUTHOR), Lavanya, Gantyada (AUTHOR), Reshmi, Ravada (AUTHOR), Dev, Kapil (AUTHOR), Kumar, Rahul (AUTHOR)
Source: European Journal of Neuroscience. Nov2022, Vol. 56 Issue 9, p5516-5531. 16p. 1 Graph.
Subjects: Alzheimer's disease, Mitochondrial pathology, Neurofibrillary tangles, Amyloid plaque, Mitochondrial membranes, Pathogenesis
Abstract: Alzheimer's disease (AD), a progressive neurodegenerative disorder, has emerged as the most common form of dementia in the elderly. Two major pathological hallmarks have been identified for AD: extracellular amyloid plaques and intracellular neurofibrillary tangles (NFT). Recently, dynamin‐related protein 1 (Drp1) was recognized to contribute significantly towards the pathogenesis of AD. Drp1 is primarily located in the cytosol, from where it translocates to the mitochondrial outer membrane and drives the mitochondrial fission via GTP hydrolysis. Drp1 interacts with Aβ and phosphorylated tau, leading to excessive mitochondrial fragmentation, which in turn results in synaptic dysfunction, neuronal damage and cognitive decline. Several studies suggest an increase in the level of Drp1 in the post‐mortem brain specimen collected from the AD patients and murine models of AD. Interestingly, heterozygous deletion of Drp1 in the transgenic murine model of AD ameliorates the mitochondrial dysfunction, improving learning and memory. The current review article discusses the possible mechanistic pathways by which Drp1 can influence the pathogenesis of AD. Besides, it will describe various inhibitors for Drp1 and their potential role as therapeutics for AD in the future. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
  Group: Ti
  Data: Mechanistic and therapeutic role of Drp1 in the pathogenesis of Alzheimer's disease.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Bera%2C+Arpita%22">Bera, Arpita</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lavanya%2C+Gantyada%22">Lavanya, Gantyada</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Reshmi%2C+Ravada%22">Reshmi, Ravada</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dev%2C+Kapil%22">Dev, Kapil</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kumar%2C+Rahul%22">Kumar, Rahul</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. Nov2022, Vol. 56 Issue 9, p5516-5531. 16p. 1 Graph.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Alzheimer's+disease%22">Alzheimer's disease</searchLink><br /><searchLink fieldCode="DE" term="%22Mitochondrial+pathology%22">Mitochondrial pathology</searchLink><br /><searchLink fieldCode="DE" term="%22Neurofibrillary+tangles%22">Neurofibrillary tangles</searchLink><br /><searchLink fieldCode="DE" term="%22Amyloid+plaque%22">Amyloid plaque</searchLink><br /><searchLink fieldCode="DE" term="%22Mitochondrial+membranes%22">Mitochondrial membranes</searchLink><br /><searchLink fieldCode="DE" term="%22Pathogenesis%22">Pathogenesis</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Alzheimer's disease (AD), a progressive neurodegenerative disorder, has emerged as the most common form of dementia in the elderly. Two major pathological hallmarks have been identified for AD: extracellular amyloid plaques and intracellular neurofibrillary tangles (NFT). Recently, dynamin‐related protein 1 (Drp1) was recognized to contribute significantly towards the pathogenesis of AD. Drp1 is primarily located in the cytosol, from where it translocates to the mitochondrial outer membrane and drives the mitochondrial fission via GTP hydrolysis. Drp1 interacts with Aβ and phosphorylated tau, leading to excessive mitochondrial fragmentation, which in turn results in synaptic dysfunction, neuronal damage and cognitive decline. Several studies suggest an increase in the level of Drp1 in the post‐mortem brain specimen collected from the AD patients and murine models of AD. Interestingly, heterozygous deletion of Drp1 in the transgenic murine model of AD ameliorates the mitochondrial dysfunction, improving learning and memory. The current review article discusses the possible mechanistic pathways by which Drp1 can influence the pathogenesis of AD. Besides, it will describe various inhibitors for Drp1 and their potential role as therapeutics for AD in the future. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1111/ejn.15611
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      – Code: eng
        Text: English
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        PageCount: 16
        StartPage: 5516
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      – SubjectFull: Alzheimer's disease
        Type: general
      – SubjectFull: Mitochondrial pathology
        Type: general
      – SubjectFull: Neurofibrillary tangles
        Type: general
      – SubjectFull: Amyloid plaque
        Type: general
      – SubjectFull: Mitochondrial membranes
        Type: general
      – SubjectFull: Pathogenesis
        Type: general
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      – TitleFull: Mechanistic and therapeutic role of Drp1 in the pathogenesis of Alzheimer's disease.
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            NameFull: Bera, Arpita
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            NameFull: Lavanya, Gantyada
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            NameFull: Reshmi, Ravada
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            NameFull: Dev, Kapil
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            NameFull: Kumar, Rahul
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            – D: 01
              M: 11
              Text: Nov2022
              Type: published
              Y: 2022
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