PMID- 21741954
OWN - NLM
STAT- MEDLINE
DCOM- 20111021
LR  - 20220408
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 82
IP  - 8
DP  - 2011 Oct 15
TI  - Targeting the nicotinic alpha7 acetylcholine receptor to enhance cognition in 
      disease.
PG  - 891-903
LID - 10.1016/j.bcp.2011.06.034 [doi]
AB  - A promising drug target currently under investigation to improve cognitive 
      deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic 
      alpha7 acetylcholine receptor (alpha7nAChR). Improving cognitive impairments in 
      diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical 
      need, and the alpha7nAChR has many properties that make it an attractive therapeutic 
      target. The alpha7nAChR is a ligand gated ion channel that has particularly high 
      permeability to Ca(2+) and is expressed in key brain regions involved in 
      cognitive processes (e.g., hippocampus). The alpha7nAChRs are localized both 
      pre-synaptically, where they can regulate neurotransmitter release, and 
      post-synaptically where they can activate intracellular signaling cascades and 
      influence downstream processes involved in learning and memory. In particular, 
      activation of the alpha7nAChR with small molecule agonists enhances long-term 
      potentiation, an in vitro model of synaptic plasticity, and improves performance 
      across multiple cognitive domains in rodents, monkeys, and humans. Positive 
      allosteric modulation of the alpha7nAChR offers an alternate approach to direct 
      agonism that could prove to be particularly beneficial in certain disease 
      populations where smoking nicotine is prevalent (e.g., schizophrenia) and could 
      interfere with an orthosteric agonist approach. The current review focuses on the 
      neurobiology of the alpha7nAChR, its role in cognition and the development status of 
      some of the most promising molecules advancing for the treatment of cognitive 
      dysfunction in disease.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Wallace, Tanya L
AU  - Wallace TL
AD  - Center for Neuroscience, SRI International, 333 Ravenswood Avenue, M/S 100-69, 
      Menlo Park, CA 94025, USA. tanya.wallace@sri.com
FAU - Porter, Richard H P
AU  - Porter RH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20110702
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Cholinergic Agents)
RN  - 0 (Chrna7 protein, human)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Alzheimer Disease/*drug therapy/metabolism
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Calcium/metabolism
MH  - Cholinergic Agents/pharmacology/therapeutic use
MH  - Cognition/*drug effects
MH  - Disease Models, Animal
MH  - Drug Discovery/*methods
MH  - Humans
MH  - Memory/drug effects
MH  - Neuronal Plasticity/drug effects
MH  - Neurons/drug effects/metabolism
MH  - Receptors, Nicotinic/*metabolism/physiology
MH  - Schizophrenia/*drug therapy/metabolism
MH  - Synaptic Transmission/drug effects
MH  - alpha7 Nicotinic Acetylcholine Receptor
EDAT- 2011/07/12 06:00
MHDA- 2011/10/22 06:00
CRDT- 2011/07/12 06:00
PHST- 2011/04/15 00:00 [received]
PHST- 2011/06/18 00:00 [revised]
PHST- 2011/06/24 00:00 [accepted]
PHST- 2011/07/12 06:00 [entrez]
PHST- 2011/07/12 06:00 [pubmed]
PHST- 2011/10/22 06:00 [medline]
AID - S0006-2952(11)00418-7 [pii]
AID - 10.1016/j.bcp.2011.06.034 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2011 Oct 15;82(8):891-903. doi: 10.1016/j.bcp.2011.06.034. 
      Epub 2011 Jul 2.