Humanin and Colivelin: Neuronal‐Death‐Suppressing Peptides for Alzheimer's Disease and Amyotrophic Lateral Sclerosis

Matsuoka, Masao; Hashimoto, Yuichi; Aiso, Sadakazu; Nishimoto, Ikuo

doi:10.1111/j.1527-3458.2006.00113.x

Cited by 45 publications

(45 citation statements)

References 57 publications

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“…Colivelin, consisting of ADNF and AGA-(C8R)HNG17, exhibits its neuroprotective activity by activating both ADNF receptor-and HN receptor-mediated prosurvival pathways in vitro Matsuoka et al, 2006). 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).…”

Section: Discussionmentioning

confidence: 99%

“…The HN receptor is thought to be on the cell membrane (Hashimoto et al, 2001a, b;Nishimoto et al, 2004;Matsuoka et al, 2006) although it remains unidentified. Our recent studies have demonstrated that HN signals against ADrelevant neuronal death are intracellularly mediated by STAT3 in vitro Hashimoto et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Colivelin has been reported to exhibit its neuroprotective activity by activating the downstream prosurvival signals of putative ADNF receptor and HN receptor in vitro Matsuoka et al, 2006). To delineate the relative in vivo potency of CLN and its component peptides, we compared the effect of i.n.…”

Section: Cln's Activity Is Stronger Than Adnf or Aga-(c8r)hng17 In Vivomentioning

confidence: 99%

“…administered with CLN, ADNF, or AGA-(C8R)HNG17 because it has been shown that STAT3 is an essential effecter for intracellular signals activated by HN and its derivatives in vitro Hashimoto et al, 2005;Matsuoka et al, 2006). Short-term i.n.…”

Section: Stat3 Is Involved In Cln-mediated Inhibition Of Cholinotoxinmentioning

confidence: 99%

“…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). 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.)…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Yamada

Chiba

Sasabe

et al. 2007

Neuropsychopharmacol

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cln's Activity Is Stronger Than Adnf or Aga-(c8r)hng17 In Vivomentioning

confidence: 99%

Section: Stat3 Is Involved In Cln-mediated Inhibition Of Cholinotoxinmentioning

confidence: 99%

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

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

Zhou

Wang

et al. 2014

Hippocampus

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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.

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Murine maternal dietary restriction affects neural Humanin expression and cellular profile

Baldauf

Sondhi

Shin

et al. 2019

J of Neuroscience Research

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To understand the cellular basis for the neurodevelopmental effects of intrauterine growth restriction (IUGR), we examined the global and regional expression of various cell types within murine (Mus musculus) fetal brain. Our model employed maternal calorie restriction to 50% daily food intake from gestation day 10–19, producing IUGR offspring. Offspring had smaller head sizes with larger head:body ratios indicating a head sparing IUGR effect. IUGR fetuses at embryonic day 19 (E19) had reduced nestin (progenitors), β‐III tubulin (immature neurons), Glial fibrillary acidic protein (astrocytes), and O4 (oligodendrocytes) cell lineages via immunofluorescence quantification and a 30% reduction in cortical thickness. No difference was found in Bcl‐2 or Bax (apoptosis) between controls and IUGR, though qualitatively, immunoreactivity of doublecortin (migration) and Ki67 (proliferation) was decreased. In the interest of examining a potential therapeutic peptide, we next investigated a novel pro‐survival peptide, mouse Humanin (mHN). Ontogeny examination revealed highest mHN expression at E19, diminishing by postnatal day 15 (P15), and nearly absent in adult (3 months). Subanalysis by sex at E19 yielded higher mHN expression among males during fetal life, without significant difference between sexes postnatally. Furthermore, female IUGR mice at E19 had a greater increase in cortical mHN versus the male fetus over their respective controls. We conclude that maternal dietary restriction‐associated IUGR interferes with neural progenitors differentiating into the various cellular components populating the cerebral cortex, and reduces cerebral cortical size. mHN expression is developmental stage and sex specific, with IUGR, particularly in the females, adaptively increasing its expression toward mediating a pro‐survival approach against nutritional adversity.

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Humanin and Colivelin: Neuronal‐Death‐Suppressing Peptides for Alzheimer's Disease and Amyotrophic Lateral Sclerosis

Cited by 45 publications

References 57 publications

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

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

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

Murine maternal dietary restriction affects neural Humanin expression and cellular profile

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