NEUROCHEMISTRY OF G-PROTEIN COUPLED RECEPTORS IN DEMENTIA

Abstract

INTRODUCTION: DUE TO THE LIMITED EFFICACY OF PRESENTLY AVAILABLE THERAPEUTICS TO TREAT NEURODEGENERATIVE DEMENTIAS SUCH AS ALZHEIMER?S DISEASE (AD), SUBCORTICAL ISCHEMIC VASCULAR DEMENTIA (SIVD), MIXED DEMENTIA (MIX), LEWY BODY DEMENTIA (LBD), ADDITIONAL THERAPEUTIC TARGETS ARE NEEDED.

METHODS: RADIOLIGAND BINDING OF HISTAMINERGIC H3, CANNABINOID CB1 AND MUSCARINIC M1 AND M2 RECEPTORS WERE PERFORMED IN DEMENTIA CORTEX AND CORRELATED WITH CLINICAL FEATURES.

RESULTS: H3 AND CB1 RECEPTORS WERE PRESERVED IN AD WHILE M1 AND M2 RECEPTORS WERE INTACT IN SIVD AND MIX, AND DIFFERENTIALLY CORRELATED WITH COGNITIVE SCORES. ADDITIONALLY, M1 RECEPTORS WERE UNCOUPLED FROM G-PROTEINS IN SIVD AND MIX BUT NOT LBD.

DISCUSSION: ANTAGONISM OF H3 AND AGONISM OF CB1 RECEPTORS PRESENT POTENTIAL THERAPEUTIC TARGETS FOR DEMENTIA. WHILE M1 AND M2 RECEPTORS ARE PRESERVED, M1 RECEPTOR UNCOUPLING FROM ITS G-PROTEIN IN SIVD AND MIX BUT NOT LBD SUGGEST DIFFERENT STRATEGIES FOR THE USE OF CHOLINERGIC REPLAC