Cholecystokinin 1 Receptor (Cck1R) Activates mTORC1 signaling and is Protective to Purkinje cells in SCA Mice
Wozniak, E. A. L.; Chen, Z.; Yang, P.; Tschumperlin, T.; Berken, M.; Ingram, M.; Henzler, C.; Orr, H. T.
Show abstract
Spinocerebellar Ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia and neurodegeneration, often in cerebellar Purkinje neurons. A SCA1 mouse model, Pcp2-ATXN1[30Q]D776, has severe ataxia in absence of progressive Purkinje neuron degeneration and death. Previous RNA-seq analyses identified cerebellar up-regulation of the peptide hormone Cholecystokinin (Cck) in Pcp2-ATXN1[30Q]D776 mice. Importantly, absence of Cck1 receptor (Cck1R) in Pcp2-ATXN1[30Q]D776 mice confers a progressive disease with Purkinje neuron death. A Cck1R agonist, A71623 administered to Pcp2-ATXN1[30Q]D776;Cck-/- and Pcp2-AXTN1[82Q] mice dampened Purkinje neuron pathology and associated deficits in motor performance. In addition, A71623 administration improved motor performance of Pcp2-ATXN2[127Q] SCA2 mice. Moreover, the Cck1R agonist A71623 corrected mTORC1 signaling and improved expression of calbindin in cerebella of AXTN1[82Q] and ATXN2[127Q] mice. These results indicate that manipulation of the Cck-Cck1R pathway is a potential therapeutic target for treatment of diseases involving Purkinje neuron degeneration.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Loss of the Familial Dysautonomia gene Elp1 in cerebellar granule cell progenitors leads to ataxia in mice 94%
- TDP-43-M323K causes abnormal brain development and progressive cognitive and motor deficits associated with mislocalised and increased levels of TDP-43. 94%
- Epilepsy and neurobehavioral abnormalities in mice with a KCNB1 pathogenic variant that alters conducting and non-conducting functions of KV2.1 93%
Similar papers in this journal
- TTBK2 and primary cilia are essential for the connectivity and survival of cerebellar Purkinje neurons 96%
- A novel, ataxic mouse model of Ataxia Telangiectasia caused by a clinically relevant nonsense mutation 95%
- DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response 94%
Similar papers in this journal
- Enhanced mGluR1 function causes motor deficits and region-specific Purkinje cell dysfunction 95%
- Defective cyclophilin A induces TDP-43 proteinopathy: implications for amyotrophic lateral sclerosis and frontotemporal dementia 93%
- Gene therapy targeting the blood-brain barrier improves neurological symptoms in a model of genetic MCT8 deficiency 93%
Similar papers in this journal
- Unique molecular features and cellular responses differentiate two populations of motor cortical layer 5b neurons in a preclinical model of ALS. 94%
- Microglial homeostasis requires balanced CSF-1/CSF-2 receptor signaling 93%
- Loss of Stathmin-2, a hallmark of TDP-43-associated ALS, causes motor neuropathy 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.