Interactions of pathological proteins in neurodegenerative diseasesReport as inadecuate




Interactions of pathological proteins in neurodegenerative diseases - Download this document for free, or read online. Document in PDF available to download.

Acta Neuropathologica

, Volume 134, Issue 2, pp 187–205

First Online: 11 April 2017Received: 09 January 2017Revised: 30 March 2017Accepted: 01 April 2017

Abstract

Neurodegenerative diseases such as Alzheimer’s disease AD, frontotemporal lobar degeneration FTD, Lewy body disease LBD, Parkinson’s disease PD, and amyotrophic lateral sclerosis ALS have in common that protein aggregates represent pathological hallmark lesions. Amyloid β-protein, τ-protein, α-synuclein, and TDP-43 are the most frequently aggregated proteins in these disorders. Although they are assumed to form disease-characteristic aggregates, such as amyloid plaques and neurofibrillary tangles in AD or Lewy bodies in LBD-PD, they are not restricted to these clinical presentations. They also occur in non-diseased individuals and can co-exist in the same brain without or with a clinical picture of a distinct dementing or movement disorder. In this review, we discuss the co-existence of these pathologies and potential additive effects in the human brain as well as related functional findings on cross-seeding and molecular interactions between these aggregates-proteins. We conclude that there is evidence for interactions at the molecular level as well as for additive effects on brain damage by multiple pathologies occurring in different functionally important neurons. Based upon this information, we hypothesize a cascade of events that may explain general mechanisms in the development of neurodegenerative disorders: 1 distinct lesions are a prerequisite for the development of a distinct disease e.g., primary age-related tauopathy for AD, 2 disease-specific pathogenic events further trigger the development of a specific disease e.g., Aβ aggregation in AD that exaggerate further Aβ and AD-related τ pathology, 3 the symptomatic disease manifests, and 4 neurodegenerative co-pathologies may be either purely coincidental or more likely have influence on the disease development and-or its clinical presentation.

KeywordsAlzheimer’s disease Amyotrophic lateral sclerosis Frontotemporal lobar degeneration Lewy body Amyloid beta Tau Synuclein TDP-43 Tara L. Spires-Jones, Johannes Attems and Dietmar Rudolf Thal contributed equally to this manuscript.

Download fulltext PDF



Author: Tara L. Spires-Jones - Johannes Attems - Dietmar Rudolf Thal

Source: https://link.springer.com/







Related documents