Insights into Brain Signal Transduction can Provide Potential Molecular Targets to Approach and Manage Alzheimer’s Disease

Abstract

Mechanisms leading to neuronal cell death in human pathology are far from being fully delineated. Understanding the molecules involved in neuronal death and the timing of their recruitment might help to explain the natural history of degenerative processes, including the morphological abnormalities observed in Alzheimer's disease (AD). Moreover, it might help refine the diagnosis by defining new molecular markers as well as find effective therapies, especially for slow cognitive deficits, often associated with neurodegenerative diseases. Disturbances in signal transduction in neurons underlie human cognitive decline. Numerous studies have analyzed the different signal transduction pathways in AD, offering interesting insights into its etiology and prospective therapies. For example, studies revealed that AD is associated with abnormal neuronal Ca 2+ homeostasis, and that signal transduction pathways are involved in Ca 2+ metabolism and phosphorylative regulation of proteins. Understanding the role and timing of action of the signaling pathways recruited during the changes in brain morphology in AD progression might help elucidate the pathogenesis of the disease, paving the way for early diagnosis, prognosis refinement, and novel molecular therapeutic strategies. In this review, we discuss the different signal transduction pathways involved in AD pathogenesis.

Phosphoinositide Signal Transduction Pathway and Osteosarcoma Metastases

“…The subcellular distribution of the PLC enzymes influences their activity, suggesting specific roles for each isoform besides the cleavage of PIP2 (69)(70)(71)(72)(73). The PLC enzymes are involved in some human diseases, including the nervous system tumors (64,65) and abnormalities (64,(74)(75)(76)(77)(78)(79).…”

Phosphoinositide-Specific Phospholipases C in Psychiatric Diseases and Suicide

“…Abnormalities in signaling mechanisms were recently analyzed in the post-mortem brains of suicide-dead individuals, exciting great interest into the 5-hydroxytryptamine 2A (HT2A) receptor-linked phosphoinositide (PI) signaling system. The involvement of PI-specific Phospholipase C (PLC) enzymes, belonging to the PI system, was suggested in a number of brain disorders, including epilepsy, Huntington's disease and Alzheimer's disease [8][9][10], schizophrenia [11,12], BPD [13], MDD [14], and suicide [15]. Selected PLC isoforms were suggested to be involved in schizophrenia and BPD [11][12][13].…”