Glutamate Signaling in Benign and Malignant Disorders: Current Status,Future Perspectives,and Therapeutic Implications

Glutamate, a nonessential amino acid, is the major excitatory neurotransmitter in the central nervous system. As such, glutamate has been shown to play a role in not only neural processes, such as learning and memory, but also in bioenergetics, biosynthetic and metabolic oncogenic pathways. Glutamate has been the target of intense investigation for its involvement not only in the pathogenesis of benign neurodegenerative diseases (NDDs) such as Parkinson''s disease, Alzheimer''s disease, schizophrenia, multiple sclerosis, and amyotropic lateral sclerosis (ALS), but also in carcinogenesis and progression of malignant diseases. In addition to its intracellular activities, glutamate in secreted form is a phylogenetically conserved cell signaling molecule. Glutamate binding activates multiple major receptor families including the metabotropic glutamate receptors (mGluRs) and ionotropic glutamate receptors (iGluRs), both of which have been implicated in various signaling pathways in cancer. Inhibition of extracellular glutamate release or glutamate receptor activation via competitive or non-competitive antagonists decreases growth, migration and invasion and induces apoptosis in breast cancer, melanoma, glioma and prostate cancer cells. In this review, we discuss the current state of glutamate signaling research as it relates to benign and malignant diseases. In addition, we provide a synopsis of clinical trials using glutamate antagonists for the treatment of NDD and malignant diseases. We conclude that in addition to its potential role as a metabolic biomarker, glutamate receptors and glutamate-initiated signaling pathways may provide novel therapeutic opportunities for cancer.     

Treatment of Psychosomatic Disorders

Goals, potentialities and limitations of treatment of psychosomatic disorders are reviewed. Removal of a disturbing psychosomatic symptom may be all that can be accomplished. The bulk of patients suffering from psychosomatic disorders should be treated by physicians other than psychiatrists. Difficulties arise, owing to differences in approach, when treatment is carried out by a general physician as well as a psychiatrist. In appraising the prospects of treatment, the age on examination, intelligence, duration of illness, degree of insight, nature of illness, environmental stress and personality structure of the patients should be considered. Psychiatric measures which have been employed include: electroconvulsive therapy, psychotropic drugs, hypnosis, drug abreaction, group therapy, supportive psychotherapy and psychoanalysis. Psychoanalysis provides the best understanding of the psychodynamics of psychosomatic illness but is, for a variety of reasons, applicable only to a small number of patients. Alternations and removal of disturbing symptoms can be accomplished by the other therapeutic means.