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Vildagliptin Attenuates Huntington’s Disease through Activation of GLP-1 Receptor/PI3K/Akt/BDNF Pathway in 3-Nitropropionic Acid Rat Model

Sayed, Noha H. ; Fathy, Nevine ; Kortam, Mona A. ; Rabie, Mostafa A. ; Mohamed, Ahmed F. ; Kamel, Ahmed S.

Neurotherapeutics, 2020-01, Vol.17 (1), p.252-268 [Periódico revisado por pares]

Cham: Springer International Publishing

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Título:
Vildagliptin Attenuates Huntington’s Disease through Activation of GLP-1 Receptor/PI3K/Akt/BDNF Pathway in 3-Nitropropionic Acid Rat Model
Autor: Sayed, Noha H. ; Fathy, Nevine ; Kortam, Mona A. ; Rabie, Mostafa A. ; Mohamed, Ahmed F. ; Kamel, Ahmed S.
Assuntos: 1-Phosphatidylinositol 3-kinase ; 3-Nitropropionic acid ; Acids ; AKT protein ; Alzheimer's disease ; Animals ; Behavior, Animal - drug effects ; Biomedical and Life Sciences ; Biomedicine ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - metabolism ; Cognitive ability ; Corpus Striatum - drug effects ; Corpus Striatum - metabolism ; Corpus Striatum - pathology ; Cyclic AMP response element-binding protein ; Dipeptidyl-peptidase IV ; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage ; Disease Models, Animal ; Glial fibrillary acidic protein ; Glucagon ; Glucagon-Like Peptide-1 Receptor - metabolism ; Huntington Disease - chemically induced ; Huntington Disease - metabolism ; Huntington's disease ; Huntingtons disease ; Immunomodulation ; Laboratory animals ; Male ; Maze Learning - drug effects ; Mitochondria ; Neostriatum ; Neurobiology ; Neurodegenerative diseases ; Neurology ; Neuromodulation ; Neuroprotection ; Neurosciences ; Neurosurgery ; Neurotransmitters ; Neurotrophic factors ; Nitro Compounds - administration & dosage ; Original ; Original Article ; Parkinson's disease ; Peptidase ; Peptides ; Pharmacy ; Phosphatidylinositol 3-Kinase - metabolism ; Propionates - administration & dosage ; Proto-Oncogene Proteins c-akt - metabolism ; Rats, Wistar ; Rodents ; Rotarod Performance Test ; Signal transduction ; Signal Transduction - drug effects ; SIRT1 protein ; Survival ; TrkB receptors ; Vildagliptin - administration & dosage ; Wortmannin ; γ-Aminobutyric acid
É parte de: Neurotherapeutics, 2020-01, Vol.17 (1), p.252-268
Descrição: Vildagliptin (Vilda), a dipeptidyl peptidase-4 (DPP-4) inhibitor, has been highlighted as a promising therapeutic agent for neurodegenerative diseases as Alzheimer’s and Parkinson’s diseases. Vilda‘s effect is mostly linked to PI3K/Akt signaling in CNS. Moreover, PI3K/Akt activation reportedly enhanced survival and dampened progression of Huntington’s disease (HD). However, Vilda’s role in HD is yet to be elucidated. Thus, the aim of the study is to uncover the potentiality of Vilda in HD and unfold its link with PI3K/Akt pathway in 3-nitropropionic acid (3NP) rat model. Rats were randomly assigned into 4 groups; group 1 received saline, whereas, groups 2, 3 and 4 received 3NP (10 mg/kg/day; i.p.) for 14 days, concomitantly with Vilda (5 mg/kg/day; p.o.) in groups 3 and 4, and wortmannin (WM), a PI3K inhibitor, (15 μg/kg/day; i.v.) in group 4. Vilda improved cognitive and motor perturbations induced by 3NP, as confirmed by striatal histopathological specimens and immunohistochemical examination of GFAP. The molecular signaling of Vilda was estimated by elevation of GLP-1 level and protein expressions of survival proteins; p85/p55 ( p Y458/199)-PI3K, p S473-Akt. Together, it boosted striatal neurotrophic factors and receptor; p S133-CREB, BDNF, p Y515-TrKB, which subsequently maintained mitochondrial integrity, as indicated by enhancing both SDH and COX activities, and the redox modulators; Sirt1, Nrf2. Such neuroprotection restored imbalance of neurotransmitters through increasing GABA and suppressing glutamate as well PDE10A. These effects were reversed by WM pre-administration. In conclusion, Vilda purveyed significant anti-Huntington effect which may be mediated, at least in part, via activation of GLP-1/PI3K/Akt pathway in 3NP rat model.
Editor: Cham: Springer International Publishing
Idioma: Inglês

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Vildagliptin Attenuates Huntington’s Disease through Activation of GLP-1 Receptor/PI3K/Akt/BDNF Pathway in 3-Nitropropionic Acid Rat Model

Sayed, Noha H. ; Fathy, Nevine ; Kortam, Mona A. ; Rabie, Mostafa A. ; Mohamed, Ahmed F. ; Kamel, Ahmed S.

Cham: Springer International Publishing

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