Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery Is the Core.

Vacchi, Elena; Kaelin-Lang, Alain; Melli, Giorgia (2020). Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery Is the Core. International journal of molecular sciences, 21(14) Molecular Diversity Preservation International MDPI 10.3390/ijms21145030

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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.

Item Type:

Journal Article (Review Article)


04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Kaelin, Alain


600 Technology > 610 Medicine & health




Molecular Diversity Preservation International MDPI




Chantal Kottler

Date Deposited:

30 Dec 2020 16:19

Last Modified:

30 Dec 2020 16:19

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Alzheimer’s disease Big tau Parkinson’s disease alpha-synuclein axonal degeneration intrinsically disordered proteins neurodegenerative disorders peripheral nervous system proteinopathies tau





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