Intranasal Administration of Forskolin and Noopept Reverses Parkinsonian Pathology in PINK1 Knockout Rats.
Intranasal Administration of Forskolin and Noopept Reverses Parkinsonian Pathology in PINK1 Knockout Rats.
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DOI：
10.3390/ijms24010690
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发表时间：
2022-12-30
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
Parkinson’s Disease (PD) is a brain-degenerative disorder characterized by a progressive loss of midbrain dopamine neurons. Current standard-of-care includes oral administration of Levodopa to address motor symptoms, but this treatment is not disease-modifying. A reduction in Protein Kinase A (PKA) signaling and neurotrophic support contributes to PD pathology. We previously showed that enhancing PKA activity in the brain via intraperitoneal administration of Forskolin in Parkinsonian rats (PINK1 knockout) abrogate motor symptoms and loss of midbrain dopamine neurons. Given that intraperitoneal administration is invasive, we hypothesized that intranasal administration of Forskolin and a second nootropic agent (Noopept) could reverse PD pathology efficiently. Results show that intranasal administration of a formulation (CNS/CT-001) containing Forskolin (10 µM) and Noopept (20 nM) significantly reversed motor symptoms, loss of hind limb strength, and neurodegeneration of midbrain dopamine neurons in PINK1-KO rats and is indistinguishable from wild-type (WT) rats; therapeutic effects associated with increased PKA activity and levels of BDNF and NGF in the brain. Intranasal administration of CNS/CT-001, but not Forskolin, significantly decreased the number of α-synuclein aggregates in the cortex of PINK1-KO rats, and is indistinguishable from WT rats. Overall, we show proof of concept that intranasal administration of CNS/CT-001 is a non-invasive, disease-modifying formulation for PD.
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影响因子：
5.3
作者：
Bondarenko O;Saarma M
通讯作者：
Saarma M
影响因子：
4.1
作者：
Dagda RK;Das Banerjee T
通讯作者：
Das Banerjee T
线粒体质量控制：有关帕金森氏病与pink1，Parkin和Omi/Htra2相关的见解，以保持线粒体稳态。
影响因子：
3
作者：
Dagda, Ruben K.;Chu, Charleen T.
通讯作者：
Chu, Charleen T.
影响因子：
3
作者：
Elahi, Behzad;Phielipp, Nicolas;Chen, Robert
通讯作者：
Chen, Robert
影响因子：
0.7
作者：
Boiko, SS;Ostrovskaya, RU;Seredenin, SB
通讯作者：
Seredenin, SB