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GM6 Attenuates Alzheimer’s Disease Pathology in APP Mice

  • Jin Yu
  • Hong Zhu
  • Saeid Taheri
  • William Mondy
  • Cheryl Kirstein
  • William Swindell
  • Dorothy Ko
  • Mark S. KindyEmail author
Article
  • 162 Downloads

Abstract

Alzheimer’s disease (AD) results in the deposition of amyloid β (Aβ) peptide into amyloid fibrils and tau into neurofibrillary tangles. Regardless of whether or not these entities are a cause or consequence of the disease process, preventing their accumulation or accelerating their clearance may slow the rate of AD onset. Motoneuronotrophic factor (MNTF) is an endogenous neurotrophin that is specific for the human nervous system, and some of the observed effects of MNTF include motoneuron differentiation, maintenance, survival, and reinnervation of target muscles and organs. GM6 is a six-amino-acid component of MNTF that appears to replicate its activity spectrum. In this study, we investigated the effect of GM6 in a mouse model of AD before the development of amyloid plaques and determined how this treatment affected the accumulation of Aβ peptide and related pathologic changes (e.g., inflammation, nerve growth factor (NGF) expression, cathepsin B, and memory impairment). Application of GM6 over a 4-month period in young APP/ΔPS1 double-transgenic mice resulted in attenuation in Aβ peptide levels, reduction of inflammation and amyloid load, increased cathepsin B expression, and improved spatial orientation. In addition, treatment with GM6 increased brain NGF levels and tempered memory impairment by ∼ 50% at the highest dose. These data suggest that GM6 may modulate disease-determining pathways at an early stage to slow the histological and clinical progression of AD.

Keywords

Alzheimer’s Aβ peptide Behavior Cathepsin B Nerve growth factor 

Notes

Acknowledgements

We would like to thank Winston Ko for his support of the studies.

Author Contribution

Conceived and designed the experiments: JY, ST, CK, DK, and MSK. Performed the experiments: JY, HZ, ST, WM, and MSK. Performed data analysis: CK and MSK. Contributed reagents/materials/analysis tools: DK. Wrote and contributed to the writing of the manuscript: CK, DK, and MSK. All authors discussed the results and edited the manuscript.

Funding Information

This work was partially supported by grants from the National Institutes of Health (R01 ES016774-01, R21AG043718, 1P20GM109091, 2P20GM103444, and 5P30GM103342), VA Merit Award (1I01RX001450-01A1), a grant from the National Science Foundation (IIP-0903795), and an AHA SFRN (15SFDRN25710468) grant (M.S.K.). Dr. Kindy is a Senior Research Career Scientist in the VA.

Compliance with Ethical Standards

This research was approved by the IACUC of the University of South Florida, following the guidelines for the Care and Use of Laboratory Animals.

Competing Interest

Dorothy Ko is an employee of Genervon and has interest in the company.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, College of PharmacyUniversity of South FloridaTampaUSA
  2. 2.Department of Psychology, College of Arts and SciencesUniversity of South FloridaTampaUSA
  3. 3.Heritage College of Osteopathic MedicineOhio UniversityAthensUSA
  4. 4.Genervon BiopharmaceuticalsMontebelloUSA
  5. 5.James A. Haley Veterans Administration Medical CenterTampaUSA
  6. 6.Shriners Hospital for ChildrenTampaUSA

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