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Review
. 2017 Jan 1;131(1):13-23.
doi: 10.1042/CS20160044.

Neurotrophin signalling: novel insights into mechanisms and pathophysiology

Mariela Mitre  1   2 , Abigail Mariga  2   3 , Moses V Chao  4   2   3
Affiliations
Review

Neurotrophin signalling: novel insights into mechanisms and pathophysiology

Mariela Mitre et al. Clin Sci (Lond). .

Abstract

Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are prominent regulators of neuronal survival, growth and differentiation during development. While trophic factors are viewed as well-understood but not innovative molecules, there are many lines of evidence indicating that BDNF plays an important role in the pathophysiology of many neurodegenerative disorders, depression, anxiety and other psychiatric disorders. In particular, lower levels of BDNF are associated with the aetiology of Alzheimer's and Huntington's diseases. A major challenge is to explain how neurotrophins are able to induce plasticity, improve learning and memory and prevent age-dependent cognitive decline through receptor signalling. This article will review the mechanism of action of neurotrophins and how BDNF/tropomyosin receptor kinase B (TrkB) receptor signaling can dictate trophic responses and change brain plasticity through activity-dependent stimulation. Alternative approaches for modulating BDNF/TrkB signalling to deliver relevant clinical outcomes in neurodegenerative and neuropsychiatric disorders will also be described.

Keywords: activity-dependent expression; deep brain stimulation; neuroprotection; neurotrophin; signalling; synaptic plasticity.

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Figures

Figure 1
Figure 1. Human BDNF expression
(A) BDNF levels shown in human donors from Allen Institute for Brain Science, Allen Human Brain Atlas [Internet]. Available from: http://human.brain-map.org. BDNF gene assessed by DNA probe A_32_P7316. (B) Neurotrophic tyrosine kinase, receptor, type 2 (NTRK2) levels shown in human donors from Allen Institute for Brain Science, Allen Human Brain Atlas [Internet]. Available from: http://human.brain-map.org. Assessed by DNA probe A_23_P216 779 in the same two donors as (A). Heatmap color represents the z-score ranging from green (low expression) through red (high expression).
See this image and copyright information in PMC

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