NDRG2: A novel Alzheimer's disease associated protein

Cathy Mitchelmore; Stine Büchmann-Møller; Lene Rask; Mark J. West; Juan C. Troncoso; Niels A. Jensen

doi:10.1016/j.nbd.2004.01.003

NDRG2: A novel Alzheimer's disease associated protein

Cathy Mitchelmore, Stine Büchmann-Møller, Lene Rask, Mark J. West, Juan C. Troncoso, Niels A. Jensen

School of Medicine

Research output: Contribution to journal › Article › peer-review

105 Scopus citations

Abstract

Our understanding of the genes involved in Alzheimer's disease (AD) is incomplete. Using subtractive cloning technology, we discovered that the α/β-hydrolase fold protein gene NDRG2 (NDRG family member 2) is upregulated at both the RNA and protein levels in AD brains. Expression of NDRG2 in affected brains was revealed in (1) cortical pyramidal neurons, (2) senile plaques and (3) cellular processes of dystrophic neurons. Overexpression of two splice variants encoding a long and short NDRG2 isoform in hippocampal pyramidal neurons of transgenic mice resulted in localization of both isoforms to dendritic processes. Taken together, our findings suggest that NDRG2 upregulation is associated with disease pathogenesis in the human brain and provide new insight into the molecular changes that occur in AD.

Original language	English (US)
Pages (from-to)	48-58
Number of pages	11
Journal	Neurobiology of Disease
Volume	16
Issue number	1
DOIs	https://doi.org/10.1016/j.nbd.2004.01.003
State	Published - Jun 2004

Keywords

Alzheimer's disease
CA1
Dystrophic neurons
Hippocampus
NDRG
Neuronal degeneration
Pyramidal neurons
Senile plaques
Transgenic mice
α/β-Hydrolase

ASJC Scopus subject areas

Neurology

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10.1016/j.nbd.2004.01.003

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@article{208ce42a9f464b4cb1eacad8f63ccebf,

title = "NDRG2: A novel Alzheimer's disease associated protein",

abstract = "Our understanding of the genes involved in Alzheimer's disease (AD) is incomplete. Using subtractive cloning technology, we discovered that the α/β-hydrolase fold protein gene NDRG2 (NDRG family member 2) is upregulated at both the RNA and protein levels in AD brains. Expression of NDRG2 in affected brains was revealed in (1) cortical pyramidal neurons, (2) senile plaques and (3) cellular processes of dystrophic neurons. Overexpression of two splice variants encoding a long and short NDRG2 isoform in hippocampal pyramidal neurons of transgenic mice resulted in localization of both isoforms to dendritic processes. Taken together, our findings suggest that NDRG2 upregulation is associated with disease pathogenesis in the human brain and provide new insight into the molecular changes that occur in AD.",

keywords = "Alzheimer's disease, CA1, Dystrophic neurons, Hippocampus, NDRG, Neuronal degeneration, Pyramidal neurons, Senile plaques, Transgenic mice, α/β-Hydrolase",

author = "Cathy Mitchelmore and Stine B{\"u}chmann-M{\o}ller and Lene Rask and West, {Mark J.} and Troncoso, {Juan C.} and Jensen, {Niels A.}",

note = "Funding Information: We thank Heidi Nielsen for excellent technical assistance with the transgenic mice. This work was supported by grants from the Lundbeck Foundation, the Novo Nordisk Foundation, the Danish Cancer Society, L{\o}vens Kemiske Fabriks Foundation, and the Michelsen Foundation. The Johns Hopkins University ADRC is supported by NIH grant AG 05146.",

year = "2004",

month = jun,

doi = "10.1016/j.nbd.2004.01.003",

language = "English (US)",

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AU - Büchmann-Møller, Stine

AU - Rask, Lene

AU - West, Mark J.

AU - Troncoso, Juan C.

AU - Jensen, Niels A.

N1 - Funding Information: We thank Heidi Nielsen for excellent technical assistance with the transgenic mice. This work was supported by grants from the Lundbeck Foundation, the Novo Nordisk Foundation, the Danish Cancer Society, Løvens Kemiske Fabriks Foundation, and the Michelsen Foundation. The Johns Hopkins University ADRC is supported by NIH grant AG 05146.

PY - 2004/6

Y1 - 2004/6

N2 - Our understanding of the genes involved in Alzheimer's disease (AD) is incomplete. Using subtractive cloning technology, we discovered that the α/β-hydrolase fold protein gene NDRG2 (NDRG family member 2) is upregulated at both the RNA and protein levels in AD brains. Expression of NDRG2 in affected brains was revealed in (1) cortical pyramidal neurons, (2) senile plaques and (3) cellular processes of dystrophic neurons. Overexpression of two splice variants encoding a long and short NDRG2 isoform in hippocampal pyramidal neurons of transgenic mice resulted in localization of both isoforms to dendritic processes. Taken together, our findings suggest that NDRG2 upregulation is associated with disease pathogenesis in the human brain and provide new insight into the molecular changes that occur in AD.

AB - Our understanding of the genes involved in Alzheimer's disease (AD) is incomplete. Using subtractive cloning technology, we discovered that the α/β-hydrolase fold protein gene NDRG2 (NDRG family member 2) is upregulated at both the RNA and protein levels in AD brains. Expression of NDRG2 in affected brains was revealed in (1) cortical pyramidal neurons, (2) senile plaques and (3) cellular processes of dystrophic neurons. Overexpression of two splice variants encoding a long and short NDRG2 isoform in hippocampal pyramidal neurons of transgenic mice resulted in localization of both isoforms to dendritic processes. Taken together, our findings suggest that NDRG2 upregulation is associated with disease pathogenesis in the human brain and provide new insight into the molecular changes that occur in AD.

KW - Alzheimer's disease

KW - CA1

KW - Dystrophic neurons

KW - Hippocampus

KW - NDRG

KW - Neuronal degeneration

KW - Pyramidal neurons

KW - Senile plaques

KW - Transgenic mice

KW - α/β-Hydrolase

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NDRG2: A novel Alzheimer's disease associated protein

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