4.5 Article

Irisin treatment lowers levels of phosphorylated tau in the hippocampus of pre-symptomatic female but not male htau mice

Journal

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
Volume 47, Issue 7, Pages 967-978

Publisher

WILEY
DOI: 10.1111/nan.12711

Keywords

Alzheimer' s disease; anti‐ inflammatory agents; dementia; metabolic diseases; neurofibrillary tangles; physical exertion; tauopathies

Funding

  1. Alan and Janice Woll Foundation
  2. Northeast Ohio Medical University

Ask authors/readers for more resources

The study shows that Irisin treatment significantly reduced ptau and TNF alpha levels in the hippocampus and serum of female htau mice, but did not have a significant effect on male htau mice.
Aims Irisin is a hormone cleaved from fibronectin type-III domain-containing protein 5 in response to exercise and may be therapeutic in Alzheimer's disease (AD). Irisin is shown to repair damage caused by midlife cardiometabolic risk factors for AD (i.e., diabetes mellitus; hypertension), prevent neural amyloid beta aggregation and reduce neuroinflammation. However, there are no investigations of irisin's effect on AD-associated tauopathy in the brain. This study begins to address this gap in knowledge. Methods Transgenic htau mice that selectively develop age-related tauopathy were treated with recombinant irisin (100 mu g/kg weekly i.p.) beginning at a pre-symptomatic age (4 months) to determine if irisin could prevent emergence of early neuropathology. One month later, mice were sacrificed to collect brain tissue and serum. Protein levels of ptau (serine 202), inflammatory cytokine tumour necrosis factor alpha (TNF alpha) and FNDC5 were quantified using capillary-based western blotting (Wes). Results Our data show that irisin treatment significantly reduced ptau and TNF alpha in the hippocampus and serum of female htau mice compared to vehicle-treated controls. Irisin treatment did not alter ptau levels in male htau hippocampus and appeared to enhance both neural and systemic TNF alpha levels. Conclusions This study provides the first evidence that enhancing the endogenous hormone irisin may be therapeutic against emerging neuropathology in a tauopathy-selective AD model. This is important because there are currently no disease-modifying therapeutics available for AD, and few agents in development address the multiple disease targets irisin appears to-making irisin an intriguing therapeutic candidate for further investigation.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available