Accumulating evidence on molecular mechanisms leading to the differentiation of neurons with retained dopaminergic fate and function suggests the induction of such differentiation as a potential form of treatment of many neurodegenerative disorders, such as Parkinson's disease (PD) and schizophrenia. Signals conveyed by the effector enzyme adenylyl cyclase (AC) appear to be important for survival or mature functioning of neurons. Indeed, although drugs interfering with this pathway have been traditionally considered to target membrane receptors coupled to G-proteins, the ACs can be thought as new interesting “druggable” target, being known to work as signaling catalysts. We discuss herein the advance of isoform-selective stimulator and/or inhibitor compounds for AC that could lead to cell-specific pharmacotherapeutics for treating dopamine (DA)-mediated disorders, including neuropsychiatric, neurodegenerative and neuroapoptotic diseases. In this context, the calcium- and DA-sensitive isoforms of AC are considered as potential key cues for dopaminergic neuronal patterning and maintenance. In particular, cell lines differentiating dopaminergic properties and expressing selective DA- and calcium-sensitive isoforms of AC are taken into account for new therapeutic and experimental tools in inducing regenerative processes or to evaluate how cAMP signals discriminate among sympatho-adrenal heterogenic lineages of neurons.
Dopamine-Responsive Isoforms of Adenylyl Cyclase as Coincidence Detectors in Development and Function of Dopaminergic Neurons
PAVAN, Barbara;DALPIAZ, Alessandro
2012
Abstract
Accumulating evidence on molecular mechanisms leading to the differentiation of neurons with retained dopaminergic fate and function suggests the induction of such differentiation as a potential form of treatment of many neurodegenerative disorders, such as Parkinson's disease (PD) and schizophrenia. Signals conveyed by the effector enzyme adenylyl cyclase (AC) appear to be important for survival or mature functioning of neurons. Indeed, although drugs interfering with this pathway have been traditionally considered to target membrane receptors coupled to G-proteins, the ACs can be thought as new interesting “druggable” target, being known to work as signaling catalysts. We discuss herein the advance of isoform-selective stimulator and/or inhibitor compounds for AC that could lead to cell-specific pharmacotherapeutics for treating dopamine (DA)-mediated disorders, including neuropsychiatric, neurodegenerative and neuroapoptotic diseases. In this context, the calcium- and DA-sensitive isoforms of AC are considered as potential key cues for dopaminergic neuronal patterning and maintenance. In particular, cell lines differentiating dopaminergic properties and expressing selective DA- and calcium-sensitive isoforms of AC are taken into account for new therapeutic and experimental tools in inducing regenerative processes or to evaluate how cAMP signals discriminate among sympatho-adrenal heterogenic lineages of neurons.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
