Nerve growth factor in metabolic complications and Alzheimer's disease: Physiology and therapeutic potential

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2020-10, Vol.1866 (10), p.165858-165858, Article 165858
• Main Authors: Ding, Xiao-Wen, Li, Rongzi, Geetha, Thangiah, Tao, Ya-Xiong, Babu, Jeganathan Ramesh
• Format: Article
• Language: English
• Subjects: Adipokines - metabolism; Alzheimer Disease - etiology; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer Disease - therapy; Alzheimer's disease; Animals; Brain - drug effects; Brain - pathology; Cell- and Tissue-Based Therapy - methods; Cognition - drug effects; Cognition - physiology; Diabetic Neuropathies - etiology; Diabetic Neuropathies - metabolism; Diabetic Neuropathies - pathology; Diabetic Neuropathies - therapy; Diabetic neuropathy; Diabetic retinopathy; Diabetic Retinopathy - etiology; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Diabetic Retinopathy - therapy; Disease Models, Animal; Genetic Therapy - methods; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Humans; Mice; Nerve Growth Factor - administration & dosage; Nerve Growth Factor - genetics; Nerve Growth Factor - metabolism; Nerve Growth Factors - metabolism; Neural Stem Cells - transplantation; NGF; Obesity; Obesity - complications; Obesity - metabolism; Obesity - pathology; Obesity - therapy; Ophthalmic Solutions - administration & dosage; Parvovirinae - genetics; proNGF; Protein Precursors - administration & dosage; Protein Precursors - metabolism; Rats; Receptor, trkA - metabolism; Signal Transduction
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2020.165858

As the population ages, obesity and metabolic complications as well as neurological disorders are becoming more prevalent, with huge economic burdens on both societies and families. New therapeutics are urgently needed. Nerve growth factor (NGF), first discovered in 1950s, is a neurotrophic factor involved in regulating cell proliferation, growth, survival, and apoptosis in both central and peripheral nervous systems. NGF and its precursor, proNGF, bind to TrkA and p75 receptors and initiate protein phosphorylation cascades, resulting in changes of cellular functions, and are associated with obesity, diabetes and its complications, and Alzheimer's disease. In this article, we summarize changes in NGF levels in metabolic and neuronal disorders, the signal transduction initiated by NGF and proNGF, the physiological and pathophysiological relevance, and therapeutic potential in treating chronic metabolic diseases and cognitive decline. •NGF is a response protein associated with changes of adipokines in obesity.•Administration and eyedrops of NGF alleviate degradation of diabetic retinal cell.•Duration of Ras/Raf activation induced by NGF determine the signal flow direction.•GSK-3 activation at different locations results in different neural functions.•NGF can be delivered into human brain via viral vector and encapsulated cell.