scholarly journals Caloric restriction blocks neuropathology and motor deficits in Machado–Joseph disease mouse models through SIRT1 pathway

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Janete Cunha-Santos ◽  
Joana Duarte-Neves ◽  
Vitor Carmona ◽  
Leonard Guarente ◽  
Luís Pereira de Almeida ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Mouse Models ◽  
Motor Deficits ◽  
Machado Joseph Disease

scholarly journals Neuropeptide Y mitigates neuropathology and motor deficits in mouse models of Machado–Joseph disease

2015 ◽  
Vol 24 (19) ◽  
pp. 5451-5463 ◽  
Author(s):  
Joana Duarte-Neves ◽  
Nélio Gonçalves ◽  
Janete Cunha-Santos ◽  
Ana Teresa Simões ◽  
Wilfred F.A. den Dunnen ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Mouse Models ◽  
Motor Deficits ◽  
Machado Joseph Disease

scholarly journals ULK overexpression mitigates motor deficits and neuropathology in mouse models of Machado-Joseph disease

2021 ◽  
Author(s):  
Ana Vasconcelos-Ferreira ◽  
Inês Morgado Martins ◽  
Diana Lobo ◽  
Dina Pereira ◽  
Miguel M. Lopes ◽  
...  
Keyword(s):  
Mouse Models ◽  
Motor Deficits ◽  
Machado Joseph Disease

P4-110: Motor deficits in mouse models of Alzheimer's disease

2012 ◽  
Vol 8 (4S_Part_18) ◽  
pp. P670-P671 ◽  
Author(s):  
Samuel Adeosun ◽  
Xu Hou ◽  
Baoying Zheng ◽  
Ian Paul ◽  
Ronald Irwin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Motor Deficits

Aberrant palmitoylation in Huntington disease

2015 ◽  
Vol 43 (2) ◽  
pp. 205-210 ◽  
Author(s):  
Shaun S. Sanders ◽  
Michael R. Hayden
Keyword(s):  
Mouse Model ◽  
Mouse Models ◽  
Huntington Disease ◽  
Motor Deficits ◽  
Adult Onset ◽  
Interacting Protein ◽  
Genetic Ablation ◽  
Neuronal Toxicity ◽  
Cag Expansion ◽  
Huntingtin Interacting Protein

Huntington disease (HD) is an adult-onset neurodegenerative disease caused by a CAG expansion in the HTT gene. HD is characterized by striatal atrophy and is associated with motor, cognitive and psychiatric deficits. In the presence of the HD mutation, the interactions between huntingtin (HTT) and huntingtin interacting protein 14 (HIP14 or DHHC17) and HIP14-like (DHHC13, a HIP14 orthologue), palmitoyl acyltransferases for HTT, are disturbed, resulting in reduced palmitoylation of HTT. Genetic ablation of either Hip14 or Hip14l recapitulates many features of HD, including striatal atrophy and motor deficits. However, there are no changes in palmitoylation of HTT in either mouse model and, subsequently, the similarities between the phenotypes of these two mouse models and the HD mouse model are believed to result from underpalmitoylation of other HIP14 and HIP14L substrates. HTT acts as a modulator of HIP14 activity such that in the presence of the HD mutation, HIP14 is less active. Consequently, HIP14 substrates are less palmitoylated, leading to neuronal toxicity. This suggests that altered HIP14–HTT and HIP14L–HTT interactions in the presence of the HD mutation reduces palmitoylation and promotes mislocalization of HTT and other HIP14/HIP14L substrates. Ultimately, HD may be, in part, a disease of altered palmitoylation.

scholarly journals Tau Reduction Does Not Prevent Motor Deficits in Two Mouse Models of Parkinson's Disease

PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e29257 ◽  
Author(s):  
Meaghan Morris ◽  
Akihiko Koyama ◽  
Eliezer Masliah ◽  
Lennart Mucke
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Models ◽  
Motor Deficits

scholarly journals Characterisation of progressive motor deficits in whisker movements in R6/2, Q175 and Hdh knock-in mouse models of Huntington’s disease

2018 ◽  
Vol 300 ◽  
pp. 103-111 ◽  
Author(s):  
Huw Garland ◽  
Nigel I. Wood ◽  
Elizabeth A. Skillings ◽  
Peter J. Detloff ◽  
A. Jennifer Morton ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Motor Deficits ◽  
Progressive Motor Deficits

scholarly journals SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate

2021 ◽  
Author(s):  
Hongfeng Zhang ◽  
Yujuan Hong ◽  
Weijie Yang ◽  
Ruimin Wang ◽  
Ting Yao ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Axonal Transport ◽  
Cerebellar Ataxia ◽  
Purkinje Cells ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
High Energy ◽  
Motor Deficits ◽  
Cell Degeneration ◽  
Mitochondrial Transport

Abstract Loss-of-function mutations in SNX14 cause autosomal recessive spinocerebellar ataxia 20, which is a form of early-onset cerebellar ataxia that lacks molecular mechanisms and mouse models. We generated Snx14-deficient mouse models and observed severe motor deficits and cell-autonomous Purkinje cell degeneration. SNX14 deficiency disrupted microtubule organization and mitochondrial transport in axons by destabilizing the microtubule-severing enzyme spastin, which is implicated in dominant hereditary spastic paraplegia with cerebellar ataxia, and compromised axonal integrity and mitochondrial function. Axonal transport disruption and mitochondrial dysfunction further led to degeneration of high-energy-demanding Purkinje cells, which resulted in the pathogenesis of cerebellar ataxia. The antiepileptic drug valproate ameliorated motor deficits and cerebellar degeneration in Snx14-deficient mice via the restoration of mitochondrial transport and function in Purkinje cells. Our study revealed an unprecedented role for SNX14-dependent axonal transport in cerebellar ataxia, demonstrated the convergence of SNX14 and spastin in mitochondrial dysfunction, and suggests valproate as a potential therapeutic agent.

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