PMID- 28210211
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 10
DP  - 2017
TI  - APP as a Protective Factor in Acute Neuronal Insults.
PG  - 22
LID - 10.3389/fnmol.2017.00022 [doi]
LID - 22
AB  - Despite its key role in the molecular pathology of Alzheimer's disease (AD), the 
      physiological function of amyloid precursor protein (APP) is unknown. Increasing 
      evidence, however, points towards a neuroprotective role of this membrane protein 
      in situations of metabolic stress. A key observation is the up-regulation of APP 
      following acute (stroke, cardiac arrest) or chronic (cerebrovascular disease) 
      hypoxic-ischemic conditions. While this mechanism may increase the risk or 
      severity of AD, APP by itself or its soluble extracellular fragment APPsalpha can 
      promote neuronal survival. Indeed, different animal models of acute 
      hypoxia-ischemia, traumatic brain injury (TBI) and excitotoxicity have revealed 
      protective effects of APP or APPsalpha. The underlying mechanisms involve 
      APP-mediated regulation of calcium homeostasis via NMDA receptors (NMDAR), 
      voltage-gated calcium channels (VGCC) or internal calcium stores. In addition, 
      APP affects the expression of survival- or apoptosis-related genes as well as 
      neurotrophic factors. In this review, we summarize the current understanding of 
      the neuroprotective role of APP and APPsalpha and possible implications for future 
      research and new therapeutic strategies.
FAU - Hefter, Dimitri
AU  - Hefter D
AD  - Institute of Physiology and Pathophysiology, Heidelberg UniversityHeidelberg, 
      Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental 
      Health, Medical Faculty Mannheim, Heidelberg UniversityMannheim, Germany.
FAU - Draguhn, Andreas
AU  - Draguhn A
AD  - Institute of Physiology and Pathophysiology, Heidelberg University Heidelberg, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170202
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC5288400
OTO - NOTNLM
OT  - Alzheimer
OT  - amyloid precursor protein
OT  - calcium toxicity
OT  - cell death
OT  - ischemia
OT  - neuroprotection
OT  - stroke
OT  - traumatic brain injury
EDAT- 2017/02/18 06:00
MHDA- 2017/02/18 06:01
PMCR- 2017/01/01
CRDT- 2017/02/18 06:00
PHST- 2016/11/07 00:00 [received]
PHST- 2017/01/16 00:00 [accepted]
PHST- 2017/02/18 06:00 [entrez]
PHST- 2017/02/18 06:00 [pubmed]
PHST- 2017/02/18 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2017.00022 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2017 Feb 2;10:22. doi: 10.3389/fnmol.2017.00022. eCollection 
      2017.