PMID- 35368248
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220405
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 16
DP  - 2022
TI  - Neuroprotective Effects of a Cholecystokinin Analogue in the 
      1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Parkinson's Disease Mouse Model.
PG  - 814430
LID - 10.3389/fnins.2022.814430 [doi]
LID - 814430
AB  - Parkinson's disease (PD) is a chronic neurodegenerative disease. Type 2 diabetes 
      mellitus (T2DM) has been identified as a risk factor for PD. Drugs originally 
      developed for T2DM treatment such as liraglutide have shown neuroprotective 
      effects in mouse models of PD. Cholecystokinin (CCK) is a peptide hormone with 
      growth factor properties. Here, we demonstrate the neuroprotective effects of the 
      (pGLu)-(Gln)-CCK8 analogue in an acute PD mouse model induced by 
      1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Administration of CCK 
      analogue (50 nmol/kg ip.) for 14 days treatment improved the locomotor and 
      exploratory activity of mice, and improved bradykinesia and movement balance of 
      mice. The CCK analogue administration also restored tyrosine hydroxylase (TH) 
      positive dopaminergic neurons number and synapse number (synaptophysin levels) in 
      the substantia nigra pars compacta (SNpc). The CCK analogue decreased glia 
      activation and neuroinflammation in the SNpc, and regulated autophagy dysfunction 
      induced by MPTP. CCK analogue protected against mitochondrial damage and ER 
      stress, and also decreased the ratio of apoptosis signaling molecules Bax/Bcl-2. 
      Importantly, the CCK analogue improved the decrease of p-CREBS(133) growth factor 
      signaling in the SNpc. Therefore, the CCK analogue promotes cell survival of 
      dopaminergic neuron in the SNpc by activating the cAMP/PKA/CREB pathway that also 
      inhibits apoptosis and regulates autophagy impairment. The present results 
      indicate that CCK analogue shows a promising potential for the treatment of PD.
CI  - Copyright (c) 2022 Zhang, Li, Su, Ma, Yuan, Yu, Shi, Shao, Zhang and Holscher.
FAU - Zhang, Zijuan
AU  - Zhang Z
AD  - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, 
      Zhengzhou, China.
AD  - School of Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 
      China.
FAU - Li, Hai
AU  - Li H
AD  - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, 
      Zhengzhou, China.
AD  - School of Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 
      China.
FAU - Su, Yunfang
AU  - Su Y
AD  - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, 
      Zhengzhou, China.
FAU - Ma, Jinlian
AU  - Ma J
AD  - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, 
      Zhengzhou, China.
FAU - Yuan, Ye
AU  - Yuan Y
AD  - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, 
      Zhengzhou, China.
FAU - Yu, Ziyang
AU  - Yu Z
AD  - School of Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 
      China.
FAU - Shi, Ming
AU  - Shi M
AD  - School of Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 
      China.
FAU - Shao, Simai
AU  - Shao S
AD  - School of Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 
      China.
FAU - Zhang, Zhenqiang
AU  - Zhang Z
AD  - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, 
      Zhengzhou, China.
FAU - Holscher, Christian
AU  - Holscher C
AD  - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, 
      Zhengzhou, China.
AD  - Neurology Department of the Second Associated Hospital of Shanxi Medical 
      University, Taiyuan, China.
LA  - eng
PT  - Journal Article
DEP - 20220315
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC8964967
OTO - NOTNLM
OT  - CCK
OT  - MPTP
OT  - Parkinson's disease
OT  - apoptosis
OT  - autophagy
OT  - insulin
OT  - neuroinflammation
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/05 06:00
MHDA- 2022/04/05 06:01
PMCR- 2022/01/01
CRDT- 2022/04/04 05:05
PHST- 2021/11/13 00:00 [received]
PHST- 2022/02/11 00:00 [accepted]
PHST- 2022/04/04 05:05 [entrez]
PHST- 2022/04/05 06:00 [pubmed]
PHST- 2022/04/05 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2022.814430 [doi]
PST - epublish
SO  - Front Neurosci. 2022 Mar 15;16:814430. doi: 10.3389/fnins.2022.814430. 
      eCollection 2022.