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Neuropep-1 ameliorates learning and memory deficits in an Alzheimer's disease mouse model, increases brain-derived neurotrophic factor expression in the brain, and causes reduction of amyloid beta plaques.
Neurobiol Aging 2014; 35(5):990-1001NA

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid beta (Aβ) deposits, hyperphosphorylated tau deposition, and cognitive dysfunction. Abnormalities in the expression of brain-derived neurotrophic factor (BDNF), which plays an important role in learning and memory formation, have been reported in the brains of AD patients. A BDNF modulating peptide (Neuropep-1) was previously identified by positional-scanning synthetic peptide combinatorial library. Here we examine the neuroprotective effects of Neuropep-1 on several in vitro neurotoxic insults, and triple-transgenic AD mouse model (3xTg-AD). Neuropep-1 protects cultured neurons against oligomeric Aβ1-42, 1-methyl-4-phenylpyridinium, and glutamate-induced neuronal cell death. Neuropep-1 injection also significantly rescues the spatial learning and memory deficits of 3xTg-AD mice compared with vehicle-treated control group. Neuropep-1 treatment markedly increases hippocampal and cortical BDNF levels. Furthermore, we found that Neuropep-1-injected 3xTg-AD mice exhibit dramatically reduced Aβ plaque deposition and Aβ levels without affecting tau pathology. Neuropep-1 treatment does not alter the expression or activity of full-length amyloid precursor protein, α-, β-, or γ-secretase, but levels of insulin degrading enzyme, an Aβ degrading enzyme, were increased. These findings suggest Neuropep-1 may be a therapeutic candidate for the treatment of AD.

Authors+Show Affiliations

Department of Biological Sciences, Sungkyunkwan University, Suwon, Gyeonggi-Do, Korea.Department of Biological Sciences, Sungkyunkwan University, Suwon, Gyeonggi-Do, Korea.Department of Biological Sciences, Sungkyunkwan University, Suwon, Gyeonggi-Do, Korea.Department of Biological Sciences, Sungkyunkwan University, Suwon, Gyeonggi-Do, Korea.Department of Biological Sciences, Sungkyunkwan University, Suwon, Gyeonggi-Do, Korea.School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-Do, Korea.School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-Do, Korea.Department of Biological Sciences, Sungkyunkwan University, Suwon, Gyeonggi-Do, Korea. Electronic address: kimkl@skku.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24268884

Citation

Shin, Min-Kyoo, et al. "Neuropep-1 Ameliorates Learning and Memory Deficits in an Alzheimer's Disease Mouse Model, Increases Brain-derived Neurotrophic Factor Expression in the Brain, and Causes Reduction of Amyloid Beta Plaques." Neurobiology of Aging, vol. 35, no. 5, 2014, pp. 990-1001.
Shin MK, Kim HG, Baek SH, et al. Neuropep-1 ameliorates learning and memory deficits in an Alzheimer's disease mouse model, increases brain-derived neurotrophic factor expression in the brain, and causes reduction of amyloid beta plaques. Neurobiol Aging. 2014;35(5):990-1001.
Shin, M. K., Kim, H. G., Baek, S. H., Jung, W. R., Park, D. I., Park, J. S., ... Kim, K. L. (2014). Neuropep-1 ameliorates learning and memory deficits in an Alzheimer's disease mouse model, increases brain-derived neurotrophic factor expression in the brain, and causes reduction of amyloid beta plaques. Neurobiology of Aging, 35(5), pp. 990-1001. doi:10.1016/j.neurobiolaging.2013.10.091.
Shin MK, et al. Neuropep-1 Ameliorates Learning and Memory Deficits in an Alzheimer's Disease Mouse Model, Increases Brain-derived Neurotrophic Factor Expression in the Brain, and Causes Reduction of Amyloid Beta Plaques. Neurobiol Aging. 2014;35(5):990-1001. PubMed PMID: 24268884.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropep-1 ameliorates learning and memory deficits in an Alzheimer's disease mouse model, increases brain-derived neurotrophic factor expression in the brain, and causes reduction of amyloid beta plaques. AU - Shin,Min-Kyoo, AU - Kim,Hong-Gi, AU - Baek,Seung-Hyun, AU - Jung,Woo-Ram, AU - Park,Dong-Ik, AU - Park,Jong-Sung, AU - Jo,Dong-Gyu, AU - Kim,Kil-Lyong, Y1 - 2013/10/29/ PY - 2013/03/09/received PY - 2013/10/04/revised PY - 2013/10/25/accepted PY - 2013/11/26/entrez PY - 2013/11/26/pubmed PY - 2014/10/7/medline KW - Alzheimer's disease KW - Amyloid beta KW - Brain-derived Neurotrophic Factor KW - Cognition KW - Peptide SP - 990 EP - 1001 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 35 IS - 5 N2 - Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid beta (Aβ) deposits, hyperphosphorylated tau deposition, and cognitive dysfunction. Abnormalities in the expression of brain-derived neurotrophic factor (BDNF), which plays an important role in learning and memory formation, have been reported in the brains of AD patients. A BDNF modulating peptide (Neuropep-1) was previously identified by positional-scanning synthetic peptide combinatorial library. Here we examine the neuroprotective effects of Neuropep-1 on several in vitro neurotoxic insults, and triple-transgenic AD mouse model (3xTg-AD). Neuropep-1 protects cultured neurons against oligomeric Aβ1-42, 1-methyl-4-phenylpyridinium, and glutamate-induced neuronal cell death. Neuropep-1 injection also significantly rescues the spatial learning and memory deficits of 3xTg-AD mice compared with vehicle-treated control group. Neuropep-1 treatment markedly increases hippocampal and cortical BDNF levels. Furthermore, we found that Neuropep-1-injected 3xTg-AD mice exhibit dramatically reduced Aβ plaque deposition and Aβ levels without affecting tau pathology. Neuropep-1 treatment does not alter the expression or activity of full-length amyloid precursor protein, α-, β-, or γ-secretase, but levels of insulin degrading enzyme, an Aβ degrading enzyme, were increased. These findings suggest Neuropep-1 may be a therapeutic candidate for the treatment of AD. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/24268884/Neuropep_1_ameliorates_learning_and_memory_deficits_in_an_Alzheimer's_disease_mouse_model_increases_brain_derived_neurotrophic_factor_expression_in_the_brain_and_causes_reduction_of_amyloid_beta_plaques_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(13)00559-9 DB - PRIME DP - Unbound Medicine ER -