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

NEUROBIOLOGY OF AGING

卷:46

Article

Connor-Robson, Natalie^1,3  Peters, Owen M.^1,4  Millership, Steven^1,5  Ninkina, Natalia^1,2  Buchman, Vladimir L.^1,2 

[1] Cardiff Univ, Sch Biosci, Sir Martin Evans Bldg,Museum Ave, Cardiff CF10 3AX, S Glam, Wales

[2] Inst Physiol Act Cpds RAS, Chernogolovka, Moscow Region, Russia

[3] Univ Oxford, Oxford Parkinsons Dis Ctr, Le Gros Clark Bldg,South Pk Rd, Oxford OX1 3QX, England

[4] Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA USA

[5] Hammersmith Hosp, MRC Clin Sci Ctr, Fac Med, Du Cane Rd, London W12 0HS, England

关键词: Synuclein;    Nigrostriatal system;    Knockout mice;    Null mutant;    Parkinson's disease;    Dopamine;   

DOI  :  10.1016/j.neurobiolaging.2016.06.020

来源: Elsevier

【 摘 要 】

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 alpha-synuclein and cannot be compensated by other family members, whereas beta-synuclein is required for efficient maintenance of animal's balance and coordination in old age. (C) 2016 The Author(s). Published by Elsevier Inc.

【 授权许可】

Free