Poul Henning Jensen

Reduced Cytosolic Calcium as an Early Decisive Cellular State in Parkinson's Disease and Synucleinopathies

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

Standard

Reduced Cytosolic Calcium as an Early Decisive Cellular State in Parkinson's Disease and Synucleinopathies. / Betzer, Cristine; Jensen, Poul Henning.

In: Frontiers in Neuroscience, Vol. 12, 819, 06.11.2018.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{ad85ad8c9d984d569f26b7a6887ae705,
title = "Reduced Cytosolic Calcium as an Early Decisive Cellular State in Parkinson's Disease and Synucleinopathies",
abstract = "The more than 30-year-old Calcium hypothesis postulates that dysregulation in calcium dependent processes in the aging brain contributes to its increased vulnerability and this concept has been extended to Alzheimer's disease and Parkinson's disease. Central to the hypothesis is that increased levels of intracellular calcium develop and contributes to neuronal demise. We have studied the impact on cells encountering a gradual build-up of aggregated α-synuclein, which is a central process to Parkinson's disease and other synucleinopathies. Surprisingly, we observed a yet unrecognized phase characterized by a reduced cytosolic calcium in cellular and neuronal models of Parkinson's disease, caused by α-synuclein aggregates activating the endoplasmic calcium ATPase, SERCA. Counteracting the initial phase with low calcium rescues the subsequent degenerative phase with increased calcium and cell death - and demonstrates this early phase initiates decisive degenerative signals. In this review, we discuss our findings in relation to literature on calcium dysregulation in Parkinson's disease and dementia.",
keywords = "Aggregation, Calcium, Dementia, Synucleinopathies, Α-synuclein",
author = "Cristine Betzer and Jensen, {Poul Henning}",
year = "2018",
month = "11",
day = "6",
doi = "10.3389/fnins.2018.00819",
language = "English",
volume = "12",
journal = "Frontiers in Neuroscience",
issn = "1662-4548",
publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Reduced Cytosolic Calcium as an Early Decisive Cellular State in Parkinson's Disease and Synucleinopathies

AU - Betzer, Cristine

AU - Jensen, Poul Henning

PY - 2018/11/6

Y1 - 2018/11/6

N2 - The more than 30-year-old Calcium hypothesis postulates that dysregulation in calcium dependent processes in the aging brain contributes to its increased vulnerability and this concept has been extended to Alzheimer's disease and Parkinson's disease. Central to the hypothesis is that increased levels of intracellular calcium develop and contributes to neuronal demise. We have studied the impact on cells encountering a gradual build-up of aggregated α-synuclein, which is a central process to Parkinson's disease and other synucleinopathies. Surprisingly, we observed a yet unrecognized phase characterized by a reduced cytosolic calcium in cellular and neuronal models of Parkinson's disease, caused by α-synuclein aggregates activating the endoplasmic calcium ATPase, SERCA. Counteracting the initial phase with low calcium rescues the subsequent degenerative phase with increased calcium and cell death - and demonstrates this early phase initiates decisive degenerative signals. In this review, we discuss our findings in relation to literature on calcium dysregulation in Parkinson's disease and dementia.

AB - The more than 30-year-old Calcium hypothesis postulates that dysregulation in calcium dependent processes in the aging brain contributes to its increased vulnerability and this concept has been extended to Alzheimer's disease and Parkinson's disease. Central to the hypothesis is that increased levels of intracellular calcium develop and contributes to neuronal demise. We have studied the impact on cells encountering a gradual build-up of aggregated α-synuclein, which is a central process to Parkinson's disease and other synucleinopathies. Surprisingly, we observed a yet unrecognized phase characterized by a reduced cytosolic calcium in cellular and neuronal models of Parkinson's disease, caused by α-synuclein aggregates activating the endoplasmic calcium ATPase, SERCA. Counteracting the initial phase with low calcium rescues the subsequent degenerative phase with increased calcium and cell death - and demonstrates this early phase initiates decisive degenerative signals. In this review, we discuss our findings in relation to literature on calcium dysregulation in Parkinson's disease and dementia.

KW - Aggregation

KW - Calcium

KW - Dementia

KW - Synucleinopathies

KW - Α-synuclein

U2 - 10.3389/fnins.2018.00819

DO - 10.3389/fnins.2018.00819

M3 - Review

C2 - 30459551

VL - 12

JO - Frontiers in Neuroscience

JF - Frontiers in Neuroscience

SN - 1662-4548

M1 - 819

ER -