Description
Colivelin is a potent synthetic peptide activator of STAT3 that has neuroprotective activity. It protects approximately 50 and 100% of mouse primary cortical neurons from cell death induced by amyloid β (1-43) (Aβ43) when used at concentrations of 10 and 100 fM, respectively. Colivelin protects against cell death induced by V642I-APP in a CaM kinase IV (CaMKIV) and STAT3-dependent manner. It increases STAT3 phosphorylation
in vitro and
in vivo, an effect that correlates with improvements in working memory. Colivelin (10 pmol every six days) rescues deficits in spatial working memory in a mouse model of Alzheimer’s disease induced by intracerebroventricular injection of Aβ25-35. It also improves motor performance and prolongs survival in a mouse model of amyotrophic lateral sclerosis (ALS).
Uses
Colivelin is a peptide that offers neuroprotective effects against Alzheimer''s Disease (AD). It is also an activator of STAT3, a transcription factor involved with the JAK2/STAT3 pathway. Aberration in this pathway is linked to the pathogenesis of AD. Neuroprotective product.
Mechanism of action
Colivelin is a humanized peptide with neuroprotective effects that has a strong ability to fight against Aβ deposition, neuronal apoptosis, and synaptic plasticity defects in neurodegenerative diseases. Its neuroprotective pathway can be related to activating the STAT3 signaling pathway by inhibiting axonal damage and neuronal death in brain tissue. In addition, Colivelin may also occur through Ca2+/calmodulin-dependent protein kinase IV mediated by ADNF.
in vivo
Colivelin (intracerebroventricular administration; 10 pmol/3 μl; 3 weeks) suppresses impairment in spatial working memory induced by repetitive intracerebroventricular injection of Aβ25-35 or Aβ1-42, in addition, it antagonizes neuronal loss in the CA1 region of hippocampus induced by hippocampal injection of Aβ1-42[1].
Colivelin (intraperitoneal administration; 1.4, 7, or 35 nM/0.21 mL; on the Y-maze testday) suppresses memory impairment caused by 3-quinuclidinyl benzilateand restricts functional memory deficit[1].
Colivelin (intraperitoneal injection; 1 mg/kg; 14 days) results in improved motor and cognitive function with time by performance of mNSS, rotarod, and corner turning test.It also reduces lesion volume and improves neurological deficits after MCAO[3].
| Animal Model: | CD-1 mice[1] |
| Dosage: | 10 pmol/3 μl |
| Administration: | Intracerebroventricular administration |
| Result: | Completely suppressed Aβ 25-35-mediated impairment in spatial working memory and increased the number of immunoreactive neurons. |
| Animal Model: | C57 mice[1] |
| Dosage: | 1.4, 7, or 35 nM/0.21mL |
| Administration: | Intraperitoneal administration |
| Result: | Protected against cholinotoxin-induced amnesia in mice. |
| Animal Model: | Male C57BL/6 mice[3] |
| Dosage: | 1 mg/kg |
| Administration: | Intraperitoneal administration |
| Result: | Protected against ischemic brain injury, and improves neurological outcomes |
References
[1] TOMOHIRO CHIBA. Development of a femtomolar-acting humanin derivative named colivelin by attaching activity-dependent neurotrophic factor to its N terminus: characterization of colivelin-mediated neuroprotection against Alzheimer’s disease-relevant insults in vitro and in vivo.[J]. Journal of Neuroscience, 2005, 25 44: 10252-10261. DOI:
10.1523/jneurosci.3348-05.2005[2] MARINA YAMADA. Nasal Colivelin Treatment Ameliorates Memory Impairment Related to Alzheimer”s Disease[J]. Neuropsychopharmacology, 2007, 33 8: 2020-2032. DOI:
10.1038/sj.npp.1301591[3] TOMOHIRO CHIBA . Colivelin prolongs survival of an ALS model mouse[J]. Biochemical and biophysical research communications, 2006, 343 3: Pages 793-798. DOI:
10.1016/j.bbrc.2006.02.184
