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<i>In Vitro</i>and<i>In Vivo</i>

Chiba, Tomohiro; Yamada, Marina; Hashimoto, Yuichi; Sato, Masamichi; Sasabe, Jumpei; Kita, Yoshiko; Terashita, Kenzo; Aiso, Sadakazu; Nishimoto, Ikuo; Matsuoka, Masao

doi:10.1523/jneurosci.3348-05.2005

Cited by 83 publications

(105 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…administration of CLN on scopolamine-induced working memory impairment in a YM (Figure 2a and b). As reported in earlier studies (Mamiya and Ukai, 2001;Chiba et al, 2005), s.c. administration of scopolamine significantly reduced the SA%, an index of the spatial working memory in YM, suggesting that scopolamine impaired the spatial working memory. Intranasal administration of CLN significantly attenuated scopolamine-induced decrease in SA% in a dose-dependent manner (Figure 2b).…”

Section: Intranasally Administered Cln Is Transported To Cns Via the supporting

confidence: 77%

“…Both HN derivatives and ADNF-related peptides have also been reported to attenuate cholinotoxin-induced memory impairment in vivo (Gozes et al, 2000;Chiba et al, 2005). We found that short-term i.n.…”

Section: Discussionsupporting

confidence: 57%

“…Colivelin (CLN), the strongest HN derivative so far developed, is a fusion peptide composed of a potent HN derivative named AGA-(C8R)HNG17 attached to the C terminus of activitydependent neurotrophic factor (ADNF) (Brenneman and Gozes, 1996;Brenneman et al, 1998;Chiba et al, 2004Chiba et al, , 2005Chiba et al, , 2006Matsuoka et al, 2006). Our earlier studies indicated that HN and CLN suppressed AD-relevant neuronal death by activating STAT3 in vitro Hashimoto et al, 2005;Matsuoka et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…It has been also demonstrated in vivo that HN derivatives, including CLN, suppress spatial working memory impairment induced by blockers to the cholinergic system or intracerebroventricular (i.c.v.) injection of toxic Ab peptides (Mamiya and Ukai, 2001;Krejcova et al, 2004;Chiba et al, 2005). Considering that both insults cause memory impairment in vivo by inducing the dysfunction of the cholinergic system without significant neuronal death, HN derivatives are likely to support cognitive function by upregulating the cholinergic neurotransmission in vivo.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Nasal Colivelin Treatment Ameliorates Memory Impairment Related to Alzheimer's Disease

Yamada

Chiba

Sasabe

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

Humanin (HN) and its derivatives, such as Colivelin (CLN), suppress neuronal death induced by insults related to Alzheimer's disease (AD) by activating STAT3 in vitro. They also ameliorate functional memory impairment of mice induced by anticholinergic drugs or soluble toxic amyloid-b (Ab) in vivo when either is directly administered into the cerebral ventricle or intraperitoneally injected. However, the mechanism underlying the in vivo effect remains uncharacterized. In addition, from the standpoint of clinical application, drug delivery methods that are less invasive and specific to the central nervous system (CNS) should be developed. In this study, we show that intranasally (i.n.) administered CLN can be successfully transferred to CNS via the olfactory bulb. Using several behavioral tests, we have demonstrated that i.n. administered CLN ameliorates memory impairment of AD models in a dose-responsive manner. Attenuation of AD-related memory impairment by HN derivatives such as CLN appears to be correlated with an increase in STAT3 phosphorylation levels in the septohippocampal region, suggesting that anti-AD activities of HN derivatives may be mediated by activation of STAT3 in vivo as they are in vitro. We further demonstrate that CLN treatment inhibits an Ab induced decrease in the number of choline acetyltransferase (ChAT)-positive neurons in the medial septum. Combined with the finding that HN derivatives upregulate mRNA expression of neuronal ChAT and vesicular acetylcholine transporter (VAChT) in vitro, it is assumed that CLN may ameliorate memory impairment of AD models by supporting cholinergic neurotransmission, which is at least partly mediated by STAT3-mediated transcriptional upregulation of ChAT and VAChT.

show abstract

Section: Intranasally Administered Cln Is Transported To Cns Via the supporting

confidence: 77%

Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nasal Colivelin Treatment Ameliorates Memory Impairment Related to Alzheimer's Disease

Yamada

Chiba

Sasabe

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…HN suppresses the neurotoxicity of various causative genes for familial AD (FAD) including FAD-related mutant PS1 and PS2 genes [17][18][19] , and inhibits the neuronal cell death caused by Aβ [20,21] . HN is also effective against cell death caused by non-AD-related insults, such as serum deprivation, prion peptide 118-135, and insulin-like growth factor binding protein 3 [22][23][24] .…”

Section: Introductionmentioning

confidence: 99%

Humanin attenuates Alzheimer-like cognitive deficits and pathological changes induced by amyloid β-peptide in rats

Chai

Duan

et al. 2014

Neurosci. Bull.

View full text Add to dashboard Cite

Amyloid β-peptide (Aβ) has been implicated as a key molecule in the neurodegenerative cascades of Alzheimer's disease (AD). Humanin (HN) is a secretory peptide that inhibits the neurotoxicity of Aβ. However, the mechanism(s) by which HN exerts its neuroprotection against Aβ-induced ADlike pathological changes and memory deficits are yet to be completely defined. In the present study, we provided evidence that treatment of rats with HN increases the number of dendritic branches and the density of dendritic spines, and upregulates pre-and post-synaptic protein levels; these effects lead to enhanced long-term potentiation and amelioration of the memory deficits induced by Aβ 1-42 . HN also attenuated Aβ 1-42 -induced tau hyperphosphorylation, apparently by inhibiting the phosphorylation of Tyr307 on the inhibitory protein phosphatase-2A (PP2A) catalytic subunit and thereby activating PP2A. HN also inhibited apoptosis and reduced the oxidative stress induced by Aβ 1-42 . These fi ndings provide novel mechanisms of action for the ability of HN to protect against Aβ 1-42 -induced AD-like pathological changes and memory defi cits.

show abstract

Colivelin ameliorates amyloid β peptide-induced impairments in spatial memory, synaptic plasticity, and calcium homeostasis in rats

Zhou

Wang

et al. 2014

Hippocampus

View full text Add to dashboard Cite

Amyloid β peptide (Aβ) has been thought to be neurotoxic and responsible for the impairment of learning and memory in Alzheimer's disease (AD). Humanin (HN), a 24 amino acid polypeptide first identified from the unaffected occipital lobe of an AD patient, is believed to be neuroprotective against the AD-related neurotoxicity. In this study, we investigated the neuroprotective effects of Colivelin (CLN), a novel HN derivative, against Aβ by using behavioral test, in vivo electrophysiological recording, and intracellular calcium imaging. Our results showed that intrahippocampal injection of CLN (0.2 nmol) effectively prevented Aβ25-35 (4 nmol)-induced deficits in spatial learning and memory of rats in Morris water maze test; the suppression of in vivo hippocampal long term potentiation (LTP) by Aβ25-35 was nearly completely prevented by CLN; in addition, CLN pretreatment also effectively inhibited Aβ25-35-induced calcium overload in primary cultured hippocampal neurons. These results indicate that CLN has significant neuroprotective properties against Aβ, and CLN may holds great promise for the treatment and prevention of AD.

show abstract

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 InsultsIn VitroandIn Vivo

Cited by 83 publications

References 49 publications

Nasal Colivelin Treatment Ameliorates Memory Impairment Related to Alzheimer's Disease

Nasal Colivelin Treatment Ameliorates Memory Impairment Related to Alzheimer's Disease

Humanin attenuates Alzheimer-like cognitive deficits and pathological changes induced by amyloid β-peptide in rats

Colivelin ameliorates amyloid β peptide-induced impairments in spatial memory, synaptic plasticity, and calcium homeostasis in rats

Contact Info

Product

Resources

About