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. Kindy

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6386-6396
Number of pages11
JournalMolecular Neurobiology
Volume56
Issue number9
DOIs
StatePublished - Sep 15 2019
Externally publishedYes

Keywords

  • Alzheimer’s
  • Aβ peptide
  • Behavior
  • Cathepsin B
  • Nerve growth factor

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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