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p75NTR: A Molecule with Multiple Functions in Amyloid-Beta Metabolism and Neurotoxicity

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Abstract

The p75 neurotrophin receptor (p75NTR) is a pan-receptor for neurotrophins including nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin 4/5. P75NTR plays a diverse role from regulating cell survival to modulating neurite outgrowth. Under some pathological conditions, p75NTR expression is activated and plays detrimental roles in disease progression. Alzheimer’s disease (AD), the most common form of dementia, is characterized by the deposition of amyloid plaques, accumulation of fibrillary tangles in neurons, neurite degeneration, loss of neurons, and a progressive loss of cognitive function. Recent studies suggest that p75NTR, also a receptor for amyloid-beta (Aβ), is a critical factor involved in the pathogenesis of AD. This chapter is to discuss the roles of p75NTR in the production of amyloid-beta (Aβ), neuronal death, neurite degeneration, tau hyperphosphorylation, cell cycle re-entry, and cognition decline, to propose that p75NTR is a potential target for the development of therapeutic drugs for AD, and to provide perspectives in developing various therapeutic strategies targeting different aspects of AD hallmarks which relate to p75NTR functions, and breaking the p75NTR-mediated positive-feedback loop which promotes the cascades in the pathogenesis of AD.

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Abbreviations

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

Aβ:

Amyloid-beta

BACE:

Beta-site APP-cleaving enzyme

BDNF:

Brain-derived neurotrophic factor

CNS:

Central nervous system

DRG:

Dorsal root ganglion

ECD:

Extracellular domain

MAG:

Myelin-associated glycoprotein

NBM:

Nucleus basalis of Meynert

NGF:

Nerve growth factor

NT:

Neurotrophin

p75NTR:

p75NTR neurotrophin receptor

PNS:

Peripheral nervous system

TACE:

TNF-alpha converting enzyme

TNF:

Tumor necrosis factor

Trk:

Tropomyosin receptor kinase

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Authors and Affiliations

  1. Department of Neurology, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Daping, Chongqing, 400042, China

    Yan-Jiang Wang & Fan Zeng

  2. Division of Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia

    Khalil Saadipour & Jian-Jun Lu

  3. School of Pharmacy and Medical Sciences, Faculty of Health Sciences, University of South Australia, Adelaide, SA, Australia

    Xin-Fu Zhou

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  1. Yan-Jiang Wang
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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

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© 2014 Springer Science+Business Media New York

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Wang, YJ., Zeng, F., Saadipour, K., Lu, JJ., Zhou, XF. (2014). p75NTR: A Molecule with Multiple Functions in Amyloid-Beta Metabolism and Neurotoxicity. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_28

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