One protein, multiple pathologies: multifaceted involvement of amyloid β in neurodegenerative disorders of the brain and retina

被引：54

作者：

Gupta, Vivek ^{[1
]}

Gupta, Veer B. ^{[2
]}

Chitranshi, Nitin ^{[1
]}

Gangoda, Sumudu ^{[1
]}

Wall, Roshana Vander ^{[1
]}

Abbasi, Mojdeh ^{[1
]}

Golzan, Mojtaba ^{[1
]}

Dheer, Yogita ^{[1
]}

Shah, Tejal ^{[2
]}

Avolio, Alberto ^{[1
]}

Chung, Roger ^{[1
]}

Martins, Ralph ^{[2
]}

Graham, Stuart ^{[1
,3
]}

机构：

[1] Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW, Australia

[2] Edith Cowan Univ, Sch Med Sci, Perth, WA, Australia

[3] Univ Sydney, Save Sight Inst, Sydney, NSW, Australia

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2016年 / 73卷 / 22期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

Neurotrophic factors; Mitochondrial impairment; Protein aggregation; Inflammation; Oxidative stress; Electroretinogram; Optical coherence tomography; Metal ions; Vascular dysfunction; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; MACULAR DEGENERATION; NEUROTROPHIC FACTOR; PRECURSOR PROTEIN; MOUSE MODEL; APOLIPOPROTEIN-E; A-BETA; OXIDATIVE STRESS; GANGLION-CELLS;

D O I：

10.1007/s00018-016-2295-x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Accumulation of amyloid beta (A beta) and its aggregates in the ageing central nervous system is regarded synonymous to Alzheimer's disease (AD) pathology. Despite unquestionable advances in mechanistic and diagnostic aspects of the disease understanding, the primary cause of A beta accumulation as well as its in vivo roles remains elusive; nonetheless, the majority of the efforts to address pathological mechanisms for therapeutic development are focused towards moderating A beta accumulation in the brain. More recently, A beta deposition has been identified in the eye and is linked with distinct age-related diseases including age-related macular degeneration, glaucoma as well as AD. Awareness of the A beta accumulation in these markedly different degenerative disorders has led to an increasing body of work exploring overlapping mechanisms, a prospective biomarker role for A beta and the potential to use retina as a model for brain related neurodegenerative disorders. Here, we present an integrated view of current understanding of the retinal A beta deposition discussing the accumulation mechanisms, anticipated impacts and outlining ameliorative approaches that can be extrapolated to the retina for potential therapeutic benefits. Further longitudinal investigations in humans and animal models will determine retinal A beta association as a potential pathognomonic, diagnostic or prognostic biomarker.

引用

页码：4279 / 4297

页数：19

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