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Text
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<a href="http://doi.org/10.1111/nan.12711" target="_blank" rel="noreferrer noopener">http://doi.org/10.1111/nan.12711</a>
ISSN
1365-2990 0305-1846
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Update Year & Number
April 2021 List
NEOMED College
NEOMED College of Pharmacy
NEOMED Department
Department of Pharmaceutical Sciences
NEOMED Student Publications
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Title
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Irisin treatment lowers levels of phosphorylated tau in the hippocampus of pre-symptomatic female but not male htau mice.
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Neuropathology And Applied Neurobiology
Date
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2021
2021-03-26
Subject
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Alzheimer disease; anti-inflammatory agents; Dementia; metabolic diseases; neurofibrillary tangles; physical exertion; tauopathies
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Bretland KA; Lin Li; Bretland KM; Smith MA; Fleming SM; Dengler-Crish CM
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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 ug/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 (TNFα) and FNDC5 were quantified using capillary-based western blotting (Wes). RESULTS: Our data show that irisin treatment significantly reduced ptau and TNFα in 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 TNFα 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.
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<a href="http://doi.org/10.1111/nan.12711" target="_blank" rel="noreferrer noopener">10.1111/nan.12711</a>
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journalArticle
2021
Alzheimer disease
Anti-Inflammatory Agents
April 2021 List
Bretland KA
Bretland KM
dementia
Dengler-Crish CM
Department of Pharmaceutical Sciences
Fleming SM
journalArticle
Lin Li
metabolic diseases
NEOMED College of Pharmacy
NEOMED College of Pharmacy Student
NEOMED Student Publications
neurofibrillary tangles
Neuropathology And Applied Neurobiology
Physical Exertion
Smith MA
Tauopathies