PMID- 28814391 OWN - NLM STAT- MEDLINE DCOM- 20171120 LR - 20200930 IS - 1522-1490 (Electronic) IS - 0363-6119 (Print) IS - 0363-6119 (Linking) VI - 313 IP - 5 DP - 2017 Nov 1 TI - Filling the void: a role for exercise-induced BDNF and brain amyloid precursor protein processing. PG - R585-R593 LID - 10.1152/ajpregu.00255.2017 [doi] AB - Inactivity, obesity, and insulin resistance are significant risk factors for the development of Alzheimer's disease (AD). Several studies have demonstrated that diet-induced obesity, inactivity, and insulin resistance exacerbate the neuropathological hallmarks of AD. The aggregation of beta-amyloid peptides is one of these hallmarks. beta-Site amyloid precursor protein-cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in amyloid precursor protein (APP) processing, leading to beta-amyloid peptide formation. Understanding how BACE1 content and activity are regulated is essential for establishing therapies aimed at reducing and/or slowing the progression of AD. Exercise training has been proven to reduce the risk of AD as well as decrease beta-amyloid production and BACE1 content and/or activity. However, these long-term interventions also result in improvements in adiposity, circulating metabolites, glucose tolerance, and insulin sensitivity making it difficult to determine the direct effects of exercise on brain APP processing. This review highlights this large void in our knowledge and discusses our current understanding of the direct of effect of exercise on beta-amyloid production. We have concentrated on the central role that brain-derived neurotrophic factor (BDNF) may play in mediating the direct effects of exercise on reducing brain BACE1 content and activity as well as beta-amyloid production. Future studies should aim to generate a greater understanding of how obesity and exercise can directly alter APP processing and AD-related pathologies. This knowledge could provide evidence-based hypotheses for designing therapies to reduce the risk of AD and dementia. CI - Copyright (c) 2017 the American Physiological Society. FAU - MacPherson, Rebecca E K AU - MacPherson REK AD - Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada rmacpherson@brocku.ca. LA - eng PT - Journal Article PT - Review DEP - 20170816 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.23.46 (BACE1 protein, human) SB - IM MH - Alzheimer Disease/etiology/metabolism/pathology/*prevention & control MH - Amyloid Precursor Protein Secretases/*metabolism MH - Amyloid beta-Protein Precursor/*metabolism MH - Animals MH - Aspartic Acid Endopeptidases/*metabolism MH - Brain/*metabolism/pathology/physiopathology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - *Exercise MH - Humans MH - Insulin Resistance MH - Obesity/complications MH - Risk Factors MH - *Risk Reduction Behavior MH - Sedentary Behavior PMC - PMC5792152 OTO - NOTNLM OT - Alzheimer's disease OT - acute exercise OT - beta-amyloid OT - beta-secretase EDAT- 2017/08/18 06:00 MHDA- 2017/11/29 06:00 PMCR- 2018/11/01 CRDT- 2017/08/18 06:00 PHST- 2017/07/10 00:00 [received] PHST- 2017/08/14 00:00 [revised] PHST- 2017/08/14 00:00 [accepted] PHST- 2017/08/18 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/08/18 06:00 [entrez] PHST- 2018/11/01 00:00 [pmc-release] AID - ajpregu.00255.2017 [pii] AID - R-00255-2017 [pii] AID - 10.1152/ajpregu.00255.2017 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2017 Nov 1;313(5):R585-R593. doi: 10.1152/ajpregu.00255.2017. Epub 2017 Aug 16.