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  1. Article ; Online: In vivo brain imaging of mitochondrial Ca

    Calvo-Rodriguez, Maria / Kharitonova, Elizabeth K / Bacskai, Brian J

    Biochimica et biophysica acta. Molecular cell research

    2021  Volume 1868, Issue 6, Page(s) 118998

    Abstract: Mitochondria are involved in a large number of essential roles related to neuronal function. ... ...

    Abstract Mitochondria are involved in a large number of essential roles related to neuronal function. Ca
    MeSH term(s) Animals ; Brain/diagnostic imaging ; Brain/metabolism ; Calcium/metabolism ; Calcium Channels/metabolism ; Calcium Signaling ; Disease Models, Animal ; Humans ; Mice ; Microscopy, Fluorescence, Multiphoton/methods ; Mitochondria/metabolism ; Neurodegenerative Diseases/diagnostic imaging ; Neurodegenerative Diseases/metabolism
    Chemical Substances Calcium Channels ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2021-03-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamcr.2021.118998
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Therapeutic Strategies to Target Calcium Dysregulation in Alzheimer's Disease.

    Calvo-Rodriguez, Maria / Kharitonova, Elizabeth K / Bacskai, Brian J

    Cells

    2020  Volume 9, Issue 11

    Abstract: Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people worldwide. Unfortunately, none of the current treatments are effective at improving cognitive function in AD patients and, therefore, there is an urgent need for ... ...

    Abstract Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people worldwide. Unfortunately, none of the current treatments are effective at improving cognitive function in AD patients and, therefore, there is an urgent need for the development of new therapies that target the early cause(s) of AD. Intracellular calcium (Ca
    MeSH term(s) Alzheimer Disease/physiopathology ; Alzheimer Disease/therapy ; Calcium/metabolism ; Calcium Signaling/immunology ; Homeostasis ; Humans
    Chemical Substances Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-11-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9112513
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Real-time imaging of mitochondrial redox reveals increased mitochondrial oxidative stress associated with amyloid β aggregates in vivo in a mouse model of Alzheimer's disease.

    Calvo-Rodriguez, Maria / Kharitonova, Elizabeth K / Snyder, Austin C / Hou, Steven S / Sanchez-Mico, Maria Virtudes / Das, Sudeshna / Fan, Zhanyun / Shirani, Hamid / Nilsson, K Peter R / Serrano-Pozo, Alberto / Bacskai, Brian J

    Molecular neurodegeneration

    2024  Volume 19, Issue 1, Page(s) 6

    Abstract: Background: Reactive oxidative stress is a critical player in the amyloid beta (Aβ) toxicity that contributes to neurodegeneration in Alzheimer's disease (AD). Damaged mitochondria are one of the main sources of reactive oxygen species and accumulate in ...

    Abstract Background: Reactive oxidative stress is a critical player in the amyloid beta (Aβ) toxicity that contributes to neurodegeneration in Alzheimer's disease (AD). Damaged mitochondria are one of the main sources of reactive oxygen species and accumulate in Aβ plaque-associated dystrophic neurites in the AD brain. Although Aβ causes neuronal mitochondria reactive oxidative stress in vitro, this has never been directly observed in vivo in the living mouse brain. Here, we tested for the first time whether Aβ plaques and soluble Aβ oligomers induce mitochondrial oxidative stress in surrounding neurons in vivo, and whether this neurotoxic effect can be abrogated using mitochondrial-targeted antioxidants.
    Methods: We expressed a genetically encoded fluorescent ratiometric mitochondria-targeted reporter of oxidative stress in mouse models of the disease and performed intravital multiphoton microscopy of neuronal mitochondria and Aβ plaques.
    Results: For the first time, we demonstrated by direct observation in the living mouse brain exacerbated mitochondrial oxidative stress in neurons after both Aβ plaque deposition and direct application of soluble oligomeric Aβ onto the brain, and determined the most likely pathological sequence of events leading to oxidative stress in vivo. Oxidative stress could be inhibited by both blocking calcium influx into mitochondria and treating with the mitochondria-targeted antioxidant SS31. Remarkably, the latter ameliorated plaque-associated dystrophic neurites without impacting Aβ plaque burden.
    Conclusions: Considering these results, combination of mitochondria-targeted compounds with other anti-amyloid beta or anti-tau therapies hold promise as neuroprotective drugs for the prevention and/or treatment of AD.
    MeSH term(s) Mice ; Animals ; Amyloid beta-Peptides/metabolism ; Alzheimer Disease/metabolism ; Oxidative Stress/physiology ; Antioxidants/pharmacology ; Antioxidants/metabolism ; Oxidation-Reduction ; Mitochondria/metabolism ; Disease Models, Animal
    Chemical Substances Amyloid beta-Peptides ; Antioxidants
    Language English
    Publishing date 2024-01-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 2244557-2
    ISSN 1750-1326 ; 1750-1326
    ISSN (online) 1750-1326
    ISSN 1750-1326
    DOI 10.1186/s13024-024-00702-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease.

    Calvo-Rodriguez, Maria / Hou, Steven S / Snyder, Austin C / Kharitonova, Elizabeth K / Russ, Alyssa N / Das, Sudeshna / Fan, Zhanyun / Muzikansky, Alona / Garcia-Alloza, Monica / Serrano-Pozo, Alberto / Hudry, Eloise / Bacskai, Brian J

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 2146

    Abstract: Mitochondria contribute to shape intraneuronal ... ...

    Abstract Mitochondria contribute to shape intraneuronal Ca
    MeSH term(s) Alzheimer Disease/metabolism ; Animals ; Blotting, Western ; Brain/metabolism ; Calcium/metabolism ; Cells, Cultured ; Cytosol/metabolism ; Immunohistochemistry ; Male ; Membrane Potential, Mitochondrial/physiology ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism ; Neurodegenerative Diseases/metabolism ; Neurons/cytology ; Neurons/metabolism
    Chemical Substances Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-05-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-16074-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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