The nicotinic receptor genes.
The causative factor(s) of Alzheimer's disease (AD) are presently unknown. However, it has been shown that the number as well as the fraction of high- to low-affinity nicotine binding sites is altered in patients suffering from this disease. This finding, along with the identification of seven genes which code for nicotinic receptors expressed in the mammalian brain, has led to the idea that one nicotinic receptor subtype may be specifically altered in AD. The present article reviews how, through a molecular genetic approach, a family of genes coding for nicotinic acetylcholine receptor subtypes was uncovered. Also discussed is the use of in situ hybridization to determine the distribution of expression of the mRNA encoding for each receptor subtype and the patch clamp technique to characterize their biophysical properties. Determination of the promoters of these genes, as well as the properties of the expressed receptor subtypes, may make it possible to design new specific nicotinic receptor subtype drugs that will treat not only the symptoms of AD but the progression of the disease process as well.
Heinemann
S
S
Molecular Neurobiology Laboratory, Salk Institute, San Diego, California.
Boulter
J
J
Connolly
J
J
Deneris
E
E
Duvoisin
R
R
Hartley
M
M
Hermans-Borgmeyer
I
I
Hollmann
M
M
O'Shea-Greenfield
A
A
Papke
R
R
D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D008969:Molecular Sequence Data; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000502:physiology
D011978:Receptors, Nicotinic