Abstract: The present invention provides a method for identifying an agent to be tested for an ability to treat a psychotic disorder in a patient in need of such treatment. The invention provides a method for screening candidate drugs for anti-psychotic drug activity, preferably atypical anti-psychotic activity, comprising contacting cells or tissues with a candidate drug, determining levels of phosphorylation of the intracellular signaling proteins, DARPP-32, ERK1, ERK2 and CREB, in said cells or tissues and determining the pattern of the levels of phosphorylation of the proteins. The pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB is, in certain embodiments, compared with the pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB in the presence of an atypical anti-psychotic drug.

Abstract: A new synapsin protein, designated synapsin III, its amino acid sequence, and its human gene have been isolated and characterized. Furthermore, isoforms of synapsin III, e.g., synapsin IIIa, IIIb and IIIc, and have isolated and characterized, and cDNA encoding these isoforms has also been isolated and characterized. The synapsin III gene is located on human chromosome 22, in the vicinity of a region previously identified as a susceptibility locus for schizophrenia. The information and experimental tools provided by this discovery can be used to generate new therapeutic agents or diagnostic assays for this new protein, its associated mRNA or its associated genomic DNA. Due to its role in neurotransmission and synaptogenesis, isoforms of synapsin III are associated with the symptoms of psychiatric diseases, especially schizophrenia.

Abstract: The role of synapsin II in both the reformation and the maintenance of synaptic connections in cultured hippocampal neurons can be the basis of therapy for neurodegenerative disorder, particularly Alzheimer disease, which involve the disruption of synapses. When synapsin II expression in neurons is blocked by antisense synapsin II oligonucleotides, the ability of hippocampal neurons to reform as well as to maintain synapses is severely disrupted. Antisense suppression of synapsin II after axon formation but immediately before synaptogenesis prevents synapse formation. Suppression of synapsin II after synaptogenesis disrupts the majority of existing synapses. Re-expression of synapsin II in synapsin deficient neurons achieved after removing the antisense oligonucleotides leads to the re-establishment of synaptic connections, providing direct evidence that synapsin II is required for the maintenance and/or restoration of synapses.

Abstract: A new synapsin protein, designated synapsin III, its amino acid sequence, and its human gene have been isolated and characterized. Furthermore, isoforms of synapsin III, e.g., synapsin IIIa, IIIb and IIIc, and have isolated and characterized, and cDNA encoding these isoforms has also been isolated and characterized. The synapsin III gene is located on human chromosome 22, in the vicinity of a region previously identified as a susceptibility locus for schizophrenia. The information and experimental tools provided by this discovery can be used to generate new therapeutic agents or diagnostic assays for this new protein, its associated mRNA or its associated genomic DNA. Due to its role in neurotransmission and synaptogenesis, isoforms of synapsin III are associated with the symptoms of psychiatric diseases, especially schizophrenia.

Abstract: A new synapsin protein, designated synapsin III, its amino acid sequence, and its human gene have been isolated and characterized. Furthermore, isoforms of synapsin III, e.g., synapsin IIIa, IIIb and IIIc, and have isolated and characterized, and cDNA encoding these isoforms has also been isolated and characterized. The synapsin III gene is located on human chromosome 22, in the vicinity of a region previously identified as a susceptibility locus for schizophrenia. The information and experimental tools provided by this discovery can be used to generate new therapeutic agents or diagnostic assays for this new protein, its associated mRNA or its associated genomic DNA. Due to its role in neurotransmission and synaptogenesis, isoforms of synapsin III are associated with the symptoms of psychiatric diseases, especially schizophrenia.

Abstract: A new synapsin protein, designated synapsin III, its amino acid sequence, and its human gene have been isolated and characterized. The synapsin III gene is located on human chromosome 22, in the vicinity of a region previously identified as a susceptibility locus for schizophrenia. The information and experimental tools provided by this discovery can be used to generate new therapeutic agents or diagnostic assays for this new protein, its associated mRNA or its associated genomic DNA. Due to its role in neurotransmission and synaptogenesis, this synapsin III is associated with the symptoms of psychiatric diseases, especially schizophrenia.

Abstract: The present invention discloses the bidirectional regulation of DARPP-32 phosphorylation by dopamine and dopamine D1 and D2 receptors. This disclosure leads to new methodology in the treatment of schizophrenia and related disorders. In addition, the present invention provides methods for identifying agents that can be used in such treatment.

Abstract: Modulators of the protein Fe65 can be utilized to affect the interaction of the protein Fe65 with the cytoplasmic domain of amyloid precursor protein and thus provide therapeutics for the treatment and/or prevention of neurodegenerative diseases, such as Alzheimer's disease and dementia.

Abstract: A knockout mouse containing a non-functional allele for the gene that naturally encodes and expresses functional DARPP-32 is disclosed. This mouse contains two non-functional alleles for the gene that naturally encodes and expresses functional DARPP-32, and therefore is unable to express functional DARPP-32. This mouse finds utility as a screening model for potential therapeutic agents useful in the treatment of schizophrenia, Parkinson's disease, and the treatment of addictions, especially those involving drugs of abuse.

Abstract: Various first messengers linked to phospholipase C, including acetylcholine and interleukin-1, regulate the production both of the secreted form of the amyloid protein precursor and of amyloid .beta.-protein. Intracellular signals which are responsible for mediating these effects have now been identified, and that activation of phospholipase C may affect APP processing by either of two pathways, one involving an increase in protein kinase C and the other an increase in cytoplasmic calcium levels. The effects of calcium on APP processing appear to be independent of protein kinase C activation. The observed effects of calcium on APP processing are of therapeutic utility in the treatment of Alzheimer-type amyloidosis.

Abstract: A method of regulating phosphorylation of proteins involved in controlling processing or function of key proteins found in intracellular neurofibrillary tangles and extracellular amyloid plaques associated with Alzheimer disease comprising introducing an effective amount of a kinase modulator or phosphatase modulator, the modulator capable of increasing or decreasing the rate of proteolytic processing, or modulating the function, of said key proteins.

Abstract: Agents which modulate or affect the intracellular trafficking and processing of proteins in the mammalian cell can be utilized to affect the trafficking and processing of APP, thereby inhibiting production of Alzheimer type amyloidosis. Particularly useful agents are chloroquine and its related derivatives such as primaquine.

Abstract: Agents which modulate or affect the intracellular trafficking and processing of proteins in the mammalian cell can be utilized to affect the trafficking and processing of APP, thereby inhibiting production of Alzheimer type amyloidosis. Particularly useful agents are chloroquine and its related derivatives such as primaquine.

Abstract: A diagnostic method for neurological and psychiatric disorders utilizes the cerebrospinal fluid incubated in the presence of 32-P labelled ATP and an appropriate protein kinase. After termination of the reaction, a sample is applied to gels for electrophoresis. Subsequent autoradiography results in a disease-specific protein pattern that can be used for diagnosis of disorders such as Alzheimer disease, Huntington disease, Parkinson disease, dystonia ataxia, schizophrenia, epilepsy brain tumors, brain irradiation, head trauma, and acute and chronic encephalitic and vascular disease.