Neuroprotection against neurodegenerative diseases: development of a novel hybrid neuroprotective peptide Colivelin.
Neuronal death is directly implicated in the pathogenesis of neurodegenerative diseases (NDDs). NDDs cannot be cured because the mechanisms underlying neuronal death are too complicated to be therapeutically suppressed. Neuroprotective factors, such as neurotrophins, certain growth factors, neurotrophic cytokines, and short neuroprotective peptides, support neuronal survival in both physiological and pathological conditions, suggesting that these factors may be good drug candidates for NDDs. We recently generated a novel neuroprotective peptide named Colivelin by attaching activity-dependent neurotrophic factor (ADNF) to the N-terminus of a potent Humanin derivative, AGA-(C8R)HNG17. HN was originally identified from an Alzheimer's disease (AD) brain as an endogenous neuroprotective peptide that suppresses ADrelevant toxicity. Colivelin protects neurons from death relevant to NDDs by activating two independent prosurvival signals: an ADNF-mediated Ca2+/calmodulin-dependent protein kinase IV pathway and an HN-mediated STAT3 pathway. The neuroprotective effect of Colivelin provides novel insights into therapy for NDDs.
Chiba
Tomohiro
T
Department of Anatomy and Pharmacology, KEIO University School of Medicine, Shinjuku-ku, Tokyo, Japan. chibat@sc.itc.keio.ac.jp
Nishimoto
Ikuo
I
Aiso
Sadakazu
S
Matsuoka
Masaaki
M
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology
C508523:Colivelin; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010455:Peptides; D011993:Recombinant Fusion Proteins; C427211:humanin