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Molecular Neurobiology

, Volume 56, Issue 4, pp 2838–2844 | Cite as

DAPK1: a Novel Pathology and Treatment Target for Alzheimer’s Disease

  • Ling-zhi Xu
  • Bing-qiu Li
  • Jian-ping JiaEmail author
Article

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease and seriously damages the health of elderly population. Clinical drug research targeting at classic pathology hallmarks, such as amyloid-β (Aβ) and tau protein, failed to achieve effective cognitive improvement, suggesting that the pathogenesis of AD is much complicated, and there are still other unknown and undetermined important factors. Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin-dependent serine/threonine kinase that plays an important role in various neuronal injury models. Mounting evidence has demonstrated that DAPK1 variants are associated with AD risk. The activation of DAPK1 is also involved in AD-related neurodegeneration in the brain. Exploring the roles of DAPK1 in AD might help us understand the pathogenic mechanisms and find a novel promising therapeutic target in AD. Therefore, in this review, we comprehensively summary the main progress of DAPK1 in the AD studies from genetic risk, neuropathological process, and clinical potential implications.

Keywords

Death-associated protein kinase 1 Alzheimer’s disease Variants Neuropathology Therapeutics 

Notes

Acknowledgments

We thank Su-xia Li from the National Institute on Drug Dependence and Peking University for the revision of this work.

Funding Information

This work was supported by Beijing Municipal Natural Science Foundation (7184215); Beijing Talents Foundation (2017000020124G251); the key project of the National Natural Science Foundation of China (81530036); the National Key Scientific Instrument and Equipment Development Project (31627803); Mission Program of Beijing Municipal Administration of Hospitals (SML20150801); Beijing Scholars Program; Beijing Brain Initiative from Beijing Municipal Science & Technology Commission (Z161100000216137); China-Canada Joint Initiative on Alzheimer’s Disease and Related Disorders (81261120571); and Beijing Municipal Commission of Health and Family Planning (PXM2017_026283_000002).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Innovation Center for Neurological Disorders, Department of Neurology, Xuan Wu HospitalCapital Medical UniversityBeijingPeople’s Republic of China
  2. 2.Beijing Key Laboratory of Geriatric Cognitive DisordersBeijingPeople’s Republic of China
  3. 3.Clinical Center for Neurodegenerative Disease and Memory ImpairmentCapital Medical UniversityBeijingPeople’s Republic of China
  4. 4.Center of Alzheimer’s DiseaseBeijing Institute for Brain DisordersBeijingPeople’s Republic of China
  5. 5.Key Laboratory of Neurodegenerative DiseasesMinistry of EducationBeijingPeople’s Republic of China
  6. 6.National Clinical Research Center for Geriatric DisordersBeijingPeople’s Republic of China

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