Synaptic dysfunction is an early hallmark of several neurodegenerative disorders as Parkinson’s disease (PD), Alzheimer’s Disease (AD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and others. Although the very different etiology of these pathologies, they have as common feature the gradual and progressive degeneration of neural cells which culminates in a disturbed neuronal communication. In the past years the search for effective therapies for these disorders has failed. This might partially be due to inadequate pharmacological targets resultant from unknown pathological and physiological mechanisms.
The remarkable discovery that adult brain has the capacity to develop new neurons, as well as new glial cells, raised the hope to restore neuronal communication. In fact, it is now accepted that adult neurogenesis occurs in specialized niches (neurogenic niches) which are under the control of several factors including neurotrophins. These neurogenic niches contain multipotent neural stem/progenitor cells (NSPCs) which can differentiate into neurons, astrocytes and oligodendrocytes. Interestingly, different brain injuries or pathologies, such as epilepsy, head traumas and stroke, induce neurogenesis and/or astrogliogenesis. This increase in neurogenesis has been proposed as an endogenous attempt to repair and reduce brain damage. On the contrary, aging and several neurodegenerative disorders promote a decrease in neurogenesis. Nevertheless, NSPC-based therapy is, to date, not yet a satisfactory strategy due to poor survival and differentiation levels, as well as reduced synaptic plasticity either after transplantation or neural injury. Therefore, it is important to study the molecular and cellular mechanisms of NSPC’s function in detail, and their potential therapeutic applicability to improve long-term survival, differentiation and synaptic integration of derived newborn neural cells.
Classically, the studies in neurodegenerative disorders are mainly focused on neuronal abnormalities, while the non-neuronal cells were almost neglected. Nevertheless, there is increasing evidence that glial cells, and in particularly astrocytes and microglia, are very important in the pathology of these disorders. Astrocytes play important roles in neuronal synaptic activity by removing the majority of glutamate present at the synapse and also by releasing modulators/transmitters that interact with neuronal receptors. Moreover, in pathological conditions astrocytes have been implicated in the onset and progression of several diseases with reactive astrogliosis a common feature. In many neurodegenerative disorders, several changes in astrocytic function have been detected, namely in calcium signaling and in the release of inflammatory molecules. Furthermore, microglia plays an important role in managing neuronal cell death, neurogenesis, and synaptic interactions, besides their involvement in immune-response generating cytokines. Most likely astrocytes and microglia are possible candidates as new pharmacological targets that can ameliorate some of the features of neurological disorders.
Synaptic dysfunction is an early hallmark of several neurodegenerative disorders as Parkinson’s disease (PD), Alzheimer’s Disease (AD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and others. Although the very different etiology of these pathologies, they have as common feature the gradual and progressive degeneration of neural cells which culminates in a disturbed neuronal communication. In the past years the search for effective therapies for these disorders has failed. This might partially be due to inadequate pharmacological targets resultant from unknown pathological and physiological mechanisms.
The remarkable discovery that adult brain has the capacity to develop new neurons, as well as new glial cells, raised the hope to restore neuronal communication. In fact, it is now accepted that adult neurogenesis occurs in specialized niches (neurogenic niches) which are under the control of several factors including neurotrophins. These neurogenic niches contain multipotent neural stem/progenitor cells (NSPCs) which can differentiate into neurons, astrocytes and oligodendrocytes. Interestingly, different brain injuries or pathologies, such as epilepsy, head traumas and stroke, induce neurogenesis and/or astrogliogenesis. This increase in neurogenesis has been proposed as an endogenous attempt to repair and reduce brain damage. On the contrary, aging and several neurodegenerative disorders promote a decrease in neurogenesis. Nevertheless, NSPC-based therapy is, to date, not yet a satisfactory strategy due to poor survival and differentiation levels, as well as reduced synaptic plasticity either after transplantation or neural injury. Therefore, it is important to study the molecular and cellular mechanisms of NSPC’s function in detail, and their potential therapeutic applicability to improve long-term survival, differentiation and synaptic integration of derived newborn neural cells.
Classically, the studies in neurodegenerative disorders are mainly focused on neuronal abnormalities, while the non-neuronal cells were almost neglected. Nevertheless, there is increasing evidence that glial cells, and in particularly astrocytes and microglia, are very important in the pathology of these disorders. Astrocytes play important roles in neuronal synaptic activity by removing the majority of glutamate present at the synapse and also by releasing modulators/transmitters that interact with neuronal receptors. Moreover, in pathological conditions astrocytes have been implicated in the onset and progression of several diseases with reactive astrogliosis a common feature. In many neurodegenerative disorders, several changes in astrocytic function have been detected, namely in calcium signaling and in the release of inflammatory molecules. Furthermore, microglia plays an important role in managing neuronal cell death, neurogenesis, and synaptic interactions, besides their involvement in immune-response generating cytokines. Most likely astrocytes and microglia are possible candidates as new pharmacological targets that can ameliorate some of the features of neurological disorders.
