Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery is the Core
In neuronal cells, tau is a microtubule-associated protein placed in axons and alpha synuclein is enriched at presynaptic terminals. They display a propensity to form pathologic aggregates, which are considered the underlying cause of Alzheimer’s and Parkinson’s diseases. Their functional impairment...
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doaj-0a6251ffc72745a7b40a6ab763f23c752020-11-25T03:05:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-01215030503010.3390/ijms21145030Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery is the CoreElena Vacchi0Alain Kaelin-Lang1Giorgia Melli2Laboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano 6807, SwitzerlandLaboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano 6807, SwitzerlandLaboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano 6807, SwitzerlandIn neuronal cells, tau is a microtubule-associated protein placed in axons and alpha synuclein is enriched at presynaptic terminals. They display a propensity to form pathologic aggregates, which are considered the underlying cause of Alzheimer’s and Parkinson’s diseases. Their functional impairment induces loss of axonal transport, synaptic and mitochondrial disarray, leading to a “dying back” pattern of degeneration, which starts at the periphery of cells. In addition, pathologic spreading of alpha-synuclein from the peripheral nervous system to the brain through anatomical connectivity has been demonstrated for Parkinson’s disease. Thus, examination of the extent and types of tau and alpha-synuclein in peripheral tissues and their relation to brain neurodegenerative diseases is of relevance since it may provide insights into patterns of protein aggregation and neurodegeneration. Moreover, peripheral nervous tissues are easily accessible in-vivo and can play a relevant role in the early diagnosis of these conditions. Up-to-date investigations of tau species in peripheral tissues are scant and have mainly been restricted to rodents, whereas, more evidence is available on alpha synuclein in peripheral tissues. Here we aim to review the literature on the functional role of tau and alpha synuclein in physiological conditions and disease at the axonal level, their distribution in peripheral tissues, and discuss possible commonalities/diversities as well as their interaction in proteinopathies.https://www.mdpi.com/1422-0067/21/14/5030tauBig taualpha-synucleinintrinsically disordered proteinsperipheral nervous systemneurodegenerative disorders |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elena Vacchi Alain Kaelin-Lang Giorgia Melli |
spellingShingle |
Elena Vacchi Alain Kaelin-Lang Giorgia Melli Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery is the Core International Journal of Molecular Sciences tau Big tau alpha-synuclein intrinsically disordered proteins peripheral nervous system neurodegenerative disorders |
author_facet |
Elena Vacchi Alain Kaelin-Lang Giorgia Melli |
author_sort |
Elena Vacchi |
title |
Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery is the Core |
title_short |
Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery is the Core |
title_full |
Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery is the Core |
title_fullStr |
Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery is the Core |
title_full_unstemmed |
Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery is the Core |
title_sort |
tau and alpha synuclein synergistic effect in neurodegenerative diseases: when the periphery is the core |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-07-01 |
description |
In neuronal cells, tau is a microtubule-associated protein placed in axons and alpha synuclein is enriched at presynaptic terminals. They display a propensity to form pathologic aggregates, which are considered the underlying cause of Alzheimer’s and Parkinson’s diseases. Their functional impairment induces loss of axonal transport, synaptic and mitochondrial disarray, leading to a “dying back” pattern of degeneration, which starts at the periphery of cells. In addition, pathologic spreading of alpha-synuclein from the peripheral nervous system to the brain through anatomical connectivity has been demonstrated for Parkinson’s disease. Thus, examination of the extent and types of tau and alpha-synuclein in peripheral tissues and their relation to brain neurodegenerative diseases is of relevance since it may provide insights into patterns of protein aggregation and neurodegeneration. Moreover, peripheral nervous tissues are easily accessible in-vivo and can play a relevant role in the early diagnosis of these conditions. Up-to-date investigations of tau species in peripheral tissues are scant and have mainly been restricted to rodents, whereas, more evidence is available on alpha synuclein in peripheral tissues. Here we aim to review the literature on the functional role of tau and alpha synuclein in physiological conditions and disease at the axonal level, their distribution in peripheral tissues, and discuss possible commonalities/diversities as well as their interaction in proteinopathies. |
topic |
tau Big tau alpha-synuclein intrinsically disordered proteins peripheral nervous system neurodegenerative disorders |
url |
https://www.mdpi.com/1422-0067/21/14/5030 |
work_keys_str_mv |
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