Role of σ1Receptors in Learning and Memory and Alzheimer's Disease-Type Dementia.
The present chapter will review the role of σ1receptor in learning and memory and neuroprotection , against Alzheimer's type dementia. σ1Receptor agonists have been tested in a variety of pharmacological and pathological models of learning impairments in rodents these last past 20 years. Their anti-amnesic effects have been explained by the wide-range modulatory role of σ1receptors on Ca2+mobilizations, neurotransmitter responses, and particularly glutamate and acetylcholine systems, and neurotrophic factors. Recent observations from genetic and pharmacological studies have shown that σ1receptor can also be targeted in neurodegenerative diseases, and particularly Alzheimer's disease . Several compounds, acting partly through the σ1receptor, have showed effective neuroprotection in transgenic mouse models of Alzheimer's disease . We will review the data and discuss the possible mechanisms of action, particularly focusing on oxidative stress and mitochondrial integrity, trophic factors and a novel hypothesis suggesting a functional interaction between the σ1receptor and α7nicotinic acetylcholine receptor. Finally, we will discuss the pharmacological peculiarities of non-selective σ1receptor ligands, now developed as neuroprotectants in Alzheimer's disease , and positive modulators, recently described and that showed efficacy against learning and memory deficits.
INSERM U1198, University of Montpellier, 34095, Montpellier, France. tangui.maurice@umontpellier.fr.
Tangui
T
Maurice
INSERM U1198, University of Montpellier, 34095, Montpellier, France.|Institute of Chemical Biology, Ilia State University, Tbilisi, 0162, GA, USA.
Nino
N
Goguadze
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D003704:Dementia / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008024:Ligands; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D017480:Receptors, sigma / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism; D000097605:Sigma-1 Receptor
D008024:Ligands; D018696:Neuroprotective Agents; D017480:Receptors, sigma; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000097605:Sigma-1 Receptor
Alzheimer’s disease; Learning and memory; Neuroprotection; Oxidative stress; Positive allosteric modulators; Sigma-1 receptor