Combinational losses of synucleins reveal their differential requirements for compensating age-dependent alterations in motor behavior and dopamine metabolism

Connor-Robson, Natalie ORCID: https://orcid.org/0000-0001-8350-6928, Peters, Owen ORCID: https://orcid.org/0000-0002-6824-0663, Millership, Steven, Ninkina, Natalia ORCID: https://orcid.org/0000-0001-8570-5648 and Buchman, Vladimir L. ORCID: https://orcid.org/0000-0002-7631-8352 2016. Combinational losses of synucleins reveal their differential requirements for compensating age-dependent alterations in motor behavior and dopamine metabolism. Neurobiology of Aging 46 , pp. 107-112. 10.1016/j.neurobiolaging.2016.06.020

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Abstract

Synucleins are involved in multiple steps of the neurotransmitter turnover but the largely normal synaptic function in young adult animals completely lacking synucleins suggests their roles are dispensable for execution of these processes. Instead, they may be utilized for boosting the efficiency of certain molecular mechanisms in presynaptic terminals, with a deficiency of synuclein proteins sensitizing to or exacerbating synaptic malfunction caused by accumulation of mild alterations, which are commonly associated with aging. Although functional redundancy within the family has been reported, it is unclear whether the remaining synucleins can fully compensate for the deficiency of a lost family member, or whether some functions are specific for a particular member. We assessed several structural and functional characteristics of the nigrostriatal system of mice lacking members of the synuclein family in every possible combination and demonstrated that stabilization of the striatal dopamine level depends on the presence of α-synuclein and cannot be compensated for by other family members, whereas β-synuclein is required for efficient maintenance of animal’s balance and coordination in old age.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine
Uncontrolled Keywords:	synuclein; nigrostriatal system; knockout mice; null mutant; Parkinson’s disease; dopamine
Publisher:	Elsevier
ISSN:	0197-4580
Date of First Compliant Deposit:	5 July 2016
Date of Acceptance:	25 June 2016
Last Modified:	22 May 2023 00:43
URI:	https://orca.cardiff.ac.uk/id/eprint/92331

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