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

Vivek Gupta, Veer B. Gupta, Nitin Chitranshi, Sumudu Gangoda, Roshana Vander Wall, Mojdeh Abbasi, Mojtaba Golzan, Yogita Dheer, Tejal Shah, Alberto Avolio, Roger Chung, Ralph Martins, Stuart Graham

Research output: Contribution to journalReview articleResearchpeer-review

Abstract

Accumulation of amyloid β (Aβ) 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 Aβ 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 Aβ accumulation in the brain. More recently, Aβ 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 Aβ accumulation in these markedly different degenerative disorders has led to an increasing body of work exploring overlapping mechanisms, a prospective biomarker role for Aβ 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 Aβ 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 Aβ association as a potential pathognomonic, diagnostic or prognostic biomarker.

LanguageEnglish
Pages4279-4297
Number of pages19
JournalCellular and Molecular Life Sciences
Volume73
Issue number22
DOIs
Publication statusPublished - 22 Jun 2016

Fingerprint

Amyloid
Neurodegenerative Diseases
Retina
Pathology
Brain
Proteins
Alzheimer Disease
Biomarkers
Macular Degeneration
Glaucoma
Central Nervous System
Animal Models
Therapeutics

Keywords

  • Electroretinogram
  • Inflammation
  • Metal ions
  • Mitochondrial impairment
  • Neurotrophic factors
  • Optical coherence tomography
  • Oxidative stress
  • Protein aggregation
  • Vascular dysfunction

Cite this

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abstract = "Accumulation of amyloid β (Aβ) 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 Aβ 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 Aβ accumulation in the brain. More recently, Aβ 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 Aβ accumulation in these markedly different degenerative disorders has led to an increasing body of work exploring overlapping mechanisms, a prospective biomarker role for Aβ 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 Aβ 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 Aβ association as a potential pathognomonic, diagnostic or prognostic biomarker.",
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One protein, multiple pathologies : multifaceted involvement of amyloid β in neurodegenerative disorders of the brain and retina. / Gupta, Vivek; Gupta, Veer B.; Chitranshi, Nitin; Gangoda, Sumudu; Vander Wall, Roshana; Abbasi, Mojdeh; Golzan, Mojtaba; Dheer, Yogita; Shah, Tejal; Avolio, Alberto; Chung, Roger; Martins, Ralph; Graham, Stuart.

In: Cellular and Molecular Life Sciences, Vol. 73, No. 22, 22.06.2016, p. 4279-4297.

Research output: Contribution to journalReview articleResearchpeer-review

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