Mitochondrial Function, Dynamics, and Permeability Transition: A Complex Love Triangle as A Possible Target for the Treatment of Brain Aging and Alzheimer's Disease
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Carola Stockburger
- Schamim Eckert
- Gunter P Eckert
- Kristina Friedland
- Walter E Mueller
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000434949600030&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3233/JAD-179915
- eISSN
- 1875-8908
- Externe Identifier
- Clarivate Analytics Document Solution ID: GJ0MX
- PubMed Identifier: 29504539
- ISSN
- 1387-2877
- Zeitschrift
- JOURNAL OF ALZHEIMERS DISEASE
- Schlüsselwörter
- Antidementia drugs
- inhibition of mitochondrial permeability transition pore function
- mitochondrial dysfunction
- therapeutic efficacy
- Paginierung
- S455 - S467
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Titel
- Mitochondrial Function, Dynamics, and Permeability Transition: A Complex Love Triangle as A Possible Target for the Treatment of Brain Aging and Alzheimer's Disease
- Sub types
- Review
- Ausgabe der Zeitschrift
- 64
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Carola Stockburger
- Schamim Eckert
- Gunter P Eckert
- Kristina Friedland
- Walter E Müller
- DOI
- 10.3233/jad-179915
- Editoren
- G Perry
- J Avila
- PI Moreira
- AA Sorensen
- M Tabaton
- eISSN
- 1875-8908
- ISSN
- 1387-2877
- Ausgabe der Veröffentlichung
- s1
- Zeitschrift
- Journal of Alzheimer's Disease
- Paginierung
- S455 - S467
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Herausgeber
- IOS Press
- Herausgeber URL
- http://dx.doi.org/10.3233/jad-179915
- Datum der Datenerfassung
- 2020
- Titel
- Mitochondrial Function, Dynamics, and Permeability Transition: A Complex Love Triangle as A Possible Target for the Treatment of Brain Aging and Alzheimer’s Disease
- Ausgabe der Zeitschrift
- 64
Data source: Crossref
- Abstract
- Because of the failure of all amyloid-β directed treatment strategies for Alzheimer's disease (AD), the concept of mitochondrial dysfunction as a major pathomechanism of the cognitive decline in aging and AD has received substantial support. Accordingly, improving mitochondrial function as an alternative strategy for new drug development became of increasing interest and many different compounds have been identified which improve mitochondrial function in preclinical in vitro and in vivo experiments. However, very few if any have been investigated in clinical trials, representing a major drawback of the mitochondria directed drug development. To overcome these problems, we used a top-down approach by investigating several older antidementia drugs with clinical evidence of therapeutic efficacy. These include EGb761® (standardized ginkgo biloba extract), piracetam, and Dimebon. All improve experimentally many aspects of mitochondrial dysfunction including mitochondrial dynamics and also improve cognition and impaired neuronal plasticity, the functionally most relevant consequences of mitochondrial dysfunction. All partially inhibit opening events of the mitochondrial permeability transition pore (mPTP) which previously has mainly been discussed as a mechanism relevant for the induction of apoptosis. However, as more recent work suggests the mPTP as a master regulator of many mitochondrial functions, our data suggest the mPTP as a possible relevant drug target within the love triangle between mPTP regulation, mitochondrial dynamics, and mitochondrial function including regulation of neuronal plasticity. Drugs interfering with mPTP function will improve not only mitochondrial impairment in aging and AD but also will have beneficial effects on impaired neuronal plasticity, the pathomechanism which correlates best with functional deficits (cognition, behavior) in aging and AD.
- Addresses
- Department of Pharmacology, University of Frankfurt/M, Biocenter, Frankfurt/Main, Germany.
- Autoren
- Carola Stockburger
- Schamim Eckert
- Gunter P Eckert
- Kristina Friedland
- Walter E Müller
- DOI
- 10.3233/jad-179915
- eISSN
- 1875-8908
- Externe Identifier
- PubMed Identifier: 29504539
- Open access
- false
- ISSN
- 1387-2877
- Ausgabe der Veröffentlichung
- s1
- Zeitschrift
- Journal of Alzheimer's disease : JAD
- Schlüsselwörter
- Brain
- Mitochondria
- Animals
- Humans
- Alzheimer Disease
- Aging
- Sprache
- eng
- Medium
- Paginierung
- S455 - S467
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Datum der Datenerfassung
- 2018
- Titel
- Mitochondrial Function, Dynamics, and Permeability Transition: A Complex Love Triangle as A Possible Target for the Treatment of Brain Aging and Alzheimer's Disease.
- Sub types
- Review
- Journal Article
- Ausgabe der Zeitschrift
- 64
Data source: Europe PubMed Central
- Abstract
- Because of the failure of all amyloid-β directed treatment strategies for Alzheimer's disease (AD), the concept of mitochondrial dysfunction as a major pathomechanism of the cognitive decline in aging and AD has received substantial support. Accordingly, improving mitochondrial function as an alternative strategy for new drug development became of increasing interest and many different compounds have been identified which improve mitochondrial function in preclinical in vitro and in vivo experiments. However, very few if any have been investigated in clinical trials, representing a major drawback of the mitochondria directed drug development. To overcome these problems, we used a top-down approach by investigating several older antidementia drugs with clinical evidence of therapeutic efficacy. These include EGb761® (standardized ginkgo biloba extract), piracetam, and Dimebon. All improve experimentally many aspects of mitochondrial dysfunction including mitochondrial dynamics and also improve cognition and impaired neuronal plasticity, the functionally most relevant consequences of mitochondrial dysfunction. All partially inhibit opening events of the mitochondrial permeability transition pore (mPTP) which previously has mainly been discussed as a mechanism relevant for the induction of apoptosis. However, as more recent work suggests the mPTP as a master regulator of many mitochondrial functions, our data suggest the mPTP as a possible relevant drug target within the love triangle between mPTP regulation, mitochondrial dynamics, and mitochondrial function including regulation of neuronal plasticity. Drugs interfering with mPTP function will improve not only mitochondrial impairment in aging and AD but also will have beneficial effects on impaired neuronal plasticity, the pathomechanism which correlates best with functional deficits (cognition, behavior) in aging and AD.
- Autoren
- Carola Stockburger
- Schamim Eckert
- Gunter P Eckert
- Kristina Friedland
- Walter E Müller
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/29504539
- DOI
- 10.3233/JAD-179915
- eISSN
- 1875-8908
- Ausgabe der Veröffentlichung
- s1
- Zeitschrift
- J Alzheimers Dis
- Schlüsselwörter
- Antidementia drugs
- inhibition of mitochondrial permeability transition pore function
- mitochondrial dysfunction
- therapeutic efficacy
- Aging
- Alzheimer Disease
- Animals
- Brain
- Humans
- Mitochondria
- Sprache
- eng
- Country
- Netherlands
- Paginierung
- S455 - S467
- PII
- JAD179915
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2019
- Titel
- Mitochondrial Function, Dynamics, and Permeability Transition: A Complex Love Triangle as A Possible Target for the Treatment of Brain Aging and Alzheimer's Disease.
- Sub types
- Journal Article
- Review
- Ausgabe der Zeitschrift
- 64
Data source: PubMed
- Beziehungen:
- Property of