Nicotine consumption is linked to improvements in cognitive functions such as attention and memory, as well as improvements in symptoms for those suffering from disorders such as anxiety, depression and schizophrenia. Furthermore, nicotinic receptors in the central nervous system have been implicated in such wildly disparate conditions such as pain and neurodegenerative disorders like Parkinson's and Alzheimer's disease. Therefore, finding pharmaceutical compounds, which act on nicotinic receptors, without the side effects of nicotine including addiction, would constitute an important advancement for mental health. With SBIR funding, we will accelerate the ongoing cell- based drug discovery process by creating improved nicotinic receptor cell lines for high throughput screening of small compound libraries. The discovery of a novel molecular handle on these receptors, allows for the selective targeting of nicotinic receptor subtypes involved in disease. We propose to recapitulate the entire receptor complex including key accessory molecules in creating high functioning cell lines that represent a more complete state of nicotinic receptors as they occur in the nervous system. This innovative approach is likely to yield a higher percentage of novel classes of pharmaceutically active compounds for lead optimization than those obtained with traditional methods. PUBLIC HEALTH RELEVANCE The aim of the proposed project is for the development of therapeutic treatments of neurological disorders with a cholinergic component. Cholinergic therapeutics are relevant in the area of cognitive disorders, anxiety disorders such as depression, dementias, schizophrenia, in pain disorders, and neurodegenerative disorders including Parkinson's disease and Alzheimer's disease (Sacco et al., 2004, Newhouse et al., 2004, Lloyd and Williams, 2000).
Thesaurus Terms: Adverse Effects; Alzheimer; Alzheimer Disease; Alzheimer Sclerosis; Alzheimer Syndrome; Alzheimer's; Alzheimer's Disease; Alzheimers Dementia; Alzheimers Disease; Amentia; Anxiety; Anxiety Disorders; Area; Assay; Attention; Bioassay; Biologic Assays; Biological; Biological Assay; Cell Line; Cell Lines, Strains; Cellline; Cells; Central Nervous System; Cessation Of Smoking; Cloning, Human; Cognition; Cognition Disorders; Complex; Consumption; Degenerative Diseases, Nervous System; Degenerative Neurologic Disorders; Dementia; Dementia, Alzheimer Type; Dementia, Primary Senile Degenerative; Dementia, Senile; Disease; Disorder; Drugs; Funding; Genes; Genus Lynx; High Throughput Assay; Human Cloning; Idiopathic Parkinson Disease; Incidence; Lead; Learning; Lewy Body Parkinson Disease; Libraries; Link; Lynx; Medication; Memory; Mental Health; Mental Hygiene; Method Loinc Axis 6; Methodology; Methods; Molecular; Moods; Nrvs-Sys; Nerve Cells; Nerve Unit; Nervous System; Nervous System Diseases; Nervous System, Cns; Nervous System Structure; Neural Cell; Neuraxis; Neurocyte; Neurodegenerative Diseases; Neurodegenerative Disorders; Neurologic Body System; Neurologic Degenerative Conditions; Neurologic Diseases, Degenerative; Neurologic Disorders; Neurologic Organ System; Neurological Disorders; Neurons; Nicotine; Nicotinic Acetylcholine Receptors; Nicotinic Receptors; Organism; Pain; Pain Disorder; Painful; Paralysis Agitans; Parkinson; Parkinson Disease; Parkinson's; Parkinson's Disease; Parkinsons Disease; Pb Element; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Preparations; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Phase; Physiologic; Physiological; Physiology; Preparation; Primary Parkinsonism; Primary Senile Degenerative Dementia; Process; Production; Property; Property, Loinc Axis 2; Psychological Health; Publishing; Pyridine, 3-(1-Methyl-2-Pyrrolidinyl)-, (S)-; Receptor Cell; Receptor Gene; Receptor Protein; Sbir; Sbirs (R43/44); Schizophrenia; Schizophrenic Disorders; Screening Procedure; Small Business Innovation Research; Small Business Innovation Research Grant; Symptoms; System; System, Loinc Axis 4; Testing; Therapeutic; Treatment Side Effects; Addiction; Assay Development; Base; Cease Smoking; Cholinergic; Chronic Neuropathic Pain; Cognitive Disease; Cognitive Disorder; Cognitive Function; Cultured Cell Line; Dementia Of The Alzheimer Type; Dementia Praecox; Depression; Disease/Disorder; Drug Discovery; Drug/Agent; Heavy Metal Pb; Heavy Metal Lead; High Throughput Screening; Improved; In Vivo; Innovate; Innovation; Innovative; Living System; Mild Cognitive Disorder; Mild Cognitive Impairment; Mild Neurocognitive Disorder; Nervous System Disorder; Neurodegenerative Illness; Neurological Disease; Neuronal; Novel; Pre-Clinical; Preclinical; Primary Degenerative Dementia; Public Health Relevance; Receptor; Receptor Function; Schizophrenic; Screening; Screenings; Senile Dementia Of The Alzheimer Type; Side Effect; Small Molecule Libraries; Smoking Cessation; Stable Cell Line; Therapeutic Development; Therapy Adverse Effect; Treatment Adverse Effect
