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 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 (NPY) intranasal delivery alleviates Machado–Joseph disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joana Duarte-Neves ◽  
Cláudia Cavadas ◽  
Luís Pereira de Almeida
Keyword(s):  
Neuropeptide Y ◽  
Intranasal Administration ◽  
Viral Vectors ◽  
Granular Layer ◽  
Body Weight Gain ◽  
Pharmacological Intervention ◽  
Mammalian Brain ◽  
Motor Deficits ◽  
Translational Approach ◽  
Machado Joseph Disease

AbstractMachado–Joseph disease (MJD) is the most common dominantly-inherited ataxia worldwide with no effective treatment to prevent, stop or alleviate its progression. Neuropeptide Y (NPY) is a neuroprotective agent widely expressed in the mammalian brain. Our previous work showed that NPY overexpression mediated by stereotaxically-injected viral vectors mitigates motor deficits and neuropathology in MJD mouse models. To pursue a less invasive translational approach, we investigated whether intranasal administration of NPY would alleviate cerebellar neuropathology and motor and balance impairments in a severe MJD transgenic mouse model. For that, a NPY solution was administered into mice nostrils 5 days a week. Upon 8 weeks of treatment, we observed a mitigation of motor and balance impairments through the analysis of mice behavioral tests (rotarod, beam walking, pole and swimming tests). This was in line with a reduction of cerebellar pathology, evidenced by a preservation of cerebellar granular layer and of Purkinje cells and reduction of mutant ataxin-3 aggregate numbers. Furthermore, intranasal administration of NPY did not alter body weight gain, food intake, amount of body fat nor cholesterol or triglycerides levels. Our findings support the translational potential of intranasal infusion of NPY as a pharmacological intervention in MJD.

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

Neuropeptide Y alleviates Machado–Joseph disease

Neuropeptides ◽  
2016 ◽  
Vol 55 ◽  
pp. 5-6
Author(s):  
Joana Duarte-Neves ◽  
Janete Cunha-Santos ◽  
Nélio Gonçalves ◽  
Ana Teresa Simões ◽  
Wilfred F.A. den Dunnen ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Machado Joseph Disease

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
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