Abstract: Methods and compounds for treating alcohol use disorder and associated diseases. Included is the administering to a subject in need there of an effective amount of a compound having a modulating effect on p75NTR.

Abstract: The present disclosure provides methods of treating or preventing a substance-related disorder using Hsp90 inhibitors, Hsp90 modulators, tyrosine hydroxylase modulators, and modulators that reduce the interaction between Hsp90 and tyrosine hydroxylase.

Abstract: The present invention provides a method of mitigating a symptom of maladaptive substance use in a subject by inhibiting H-ras. In addition, the invention provides a variety of prescreening and screening methods aimed at identifying agents that modulate a symptom of maladaptive substance use. Methods of the invention can involve assaying test agent binding to H-ras. Alternatively, test agents can be screened for their ability to alter the level of H-ras polypeptides, polynucleotides, or function. Finally, the invention also provides a diagnostic method that entails measuring one or more of these levels and determining risk for maladaptive substance use based on comparison to the corresponding level for a control population.

Abstract: This invention pertains to the discovery that brain-derived neurotrophic factor (BDNF) and its associated signaling pathway is involved in reversing and/or counteracting neuroadaptations within the mesolimbic system that contribute to the development and/or maintenance of addiction (e.g. alcohol addiction). This invention also pertains to the discovery that ibogaine activity is mediated by changes in mRNA expression of GDNF. Thus, in certain embodiments, this inventioni provides a method of mitigating one or more symptoms of substance abuse in a mammal by increasing the expression or activity of GDNF, BDNF, RACK1, and/or the dopamine D3 receptor (D3R) in said mammal.

Abstract: The present invention relates to a polypeptide composition effective to alter the activity of a first protein that interacts with a second protein, where the second protein contains at least one WD-40 region. The polypeptides of the present invention typically have between 4 and 50 amino acids whose sequence is the same as a sequence of the same length in the WD-40 region of the second protein. The invention further includes a method of altering the activity of the above described first protein. In one embodiment of the invention the polypeptide composition is effective to alter the activity of a protein kinase C, where the protein kinase C interacts with a second protein, and the second protein contains at least one WD-40 region (e.g., RACK1).

Abstract: The present invention relates to a polypeptide composition effective to alter the activity of a first protein that interacts with a second protein, where the second protein contains at least one WD-40 region. The polypeptides of the present invention typically have between 4 and 50 amino acids whose sequence is the same as a sequence of the same length in the WD-40 region of the second protein. The invention further includes a method of altering the activity of the above described first protein. In one embodiment of the invention the polypeptide composition is effective to alter the activity of a protein kinase C, where the protein kinase C interacts with a second protein, and the second protein contains at least one WD-40 region (e.g., RACK1).

Abstract: The present invention relates to a polypeptide composition effective to alter the activity of a first protein that interacts with a second protein, where the second protein contains at least one WD-40 region. The polypeptides of the present invention typically have between 4 and 50 amino acids whose sequence is the same as a sequence of the same length in the WD-40 region of the second protein. The invention further includes a method of altering the activity of the above described first protein. In one embodiment of the invention the polypeptide composition is effective to alter the activity of a protein kinase C, where the protein kinase C interacts with a second protein, and the second protein contains at least one WD-40 region (e.g., RACK1).

Abstract: Compounds having immunomodulating activity are identified using a methodology which employs TER14687, TER10311 and/or TER17210 as standards. The effect candidate compounds have on PKC-theta interaction with cognate binding proteins is measured and compared with the standards. The interaction can be measured by a variety of techniques, including assessing translocation of said PKC-theta or fragment. Kits containing the TER14687, TER10311 and/or TER17210 standards are disclosed. TER14687, TER10311 and/or TER17210 are useful in modulating the immune system in a subject by reducing T-cell activity. TER14687, TER10311, TER17210 are used as leads to develop other compounds having immunomodulating activity.

Abstract: Modulators of the immune system can be identified by determining the ability of candidate substances to affect the interaction of PKC-theta or a fragment thereof with its cognate. The interaction can be measured using binding of the cognate as an index, or can be measured using a physiological response.

Abstract: Methods for assessing libraries of candidate modulators of intracellular signaling transmission pathways are described. The methods assess the ability of candidates from the library to inhibit the binding of peptides which represent participants in the signaling pathways as either a signal-generating protein or its cognate partner binding at a noncatalytic site. Specific peptides useful in this regard have been identified.

Abstract: The present invention discloses that the fyn protein binds to the PKC-theta protein. Based on this observation, the present invention provides methods of identifying agents which can be used to modulate immune system activity by blocking fyn/PKC-theta binding and therapeutic methods using such agents.

Abstract: The present invention relates to a polypeptide composition effective to alter the activity of a first protein that interacts with a second protein, where the second protein contains at least one WD-40 region. The polypeptides of the present invention typically have between 4 and 50 amino acids whose sequence is the same as a sequence of the same length in the WD-40 region of the second protein. The invention further includes a method of altering the activity of the above described first protein. In one embodiment of the invention the polypeptide composition is effective to alter the activity of a protein kinase C, where the protein kinase C interacts with a second protein, and the second protein contains at least one WD-40 region (e.g., RACK1).