Cell grafting has been considered a therapeutic approach for Parkinson's disease(PD) since the 1980 s. The classical motor symptoms of PD are caused by the loss of dopaminergic neurons in the substantia nigra pars...Cell grafting has been considered a therapeutic approach for Parkinson's disease(PD) since the 1980 s. The classical motor symptoms of PD are caused by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrement in dopamine release in the striatum. Consequently, the therapy of celltransplantation for PD consists in grafting dopamineproducing cells directly into the brain to reestablish dopamine levels. Different cell sources have been shown to induce functional benefits on both animal models of PD and human patients. However, the observed motor improvements are highly variable between individual subjects, and the sources of this variability are not fully understood. The purpose of this review is to provide a general overview of the pioneering studies done in animal models of PD that established the basis for the first clinical trials in humans, and compare these with the latest findings to identify the most relevant aspects that remain unanswered to date. The main focus of the discussions presented here will be on the mechanisms associated with the survival and functionality of the transplants. These include the role of the dopamine released by the grafts and the capacity of the grafted cells to extend fibers and to integrate into the motor circuit. The complete understanding of these aspects will require extensive research on basic aspects of molecular and cellular physiology, together with neuronal network function, in order to uncover the real potential of cell grafting for treating PD.展开更多
Parkinson’s disease (PD) or Paralysis Agitans was first formally described in “An essay on the shaking palsy”, published in 1817 by a British physician named James Parkinson. In the late 1950’s, dopamine was relat...Parkinson’s disease (PD) or Paralysis Agitans was first formally described in “An essay on the shaking palsy”, published in 1817 by a British physician named James Parkinson. In the late 1950’s, dopamine was related with the function of the corpus striatum, thus with the control of motor function. But it was not until 1967, when the landmark study of George C. Cotzias, demonstrated that oral L-DOPA, the precursor of dopamine metabolism, was shown to induce remission of PD symptoms, that the definitive association between the two was firmly established. However, later on L-DOPA treatment began to show a loss of effectiveness and demonstrated to induce a variety of undesirable effects, the most prominent being diskinesia. As a result of this, a variety of alternative or complementary pharmacological strategies have been developed. In this chapter we review the wide variety of strategies that have been used through time, which are geared toward reducing the most disabling symptoms of PD. We additionally make some suggestions as to which are the most promising ones.展开更多
基金Supported by DGAPA-PAPIIT,No.IN207116CONACyT,No.179927
文摘Cell grafting has been considered a therapeutic approach for Parkinson's disease(PD) since the 1980 s. The classical motor symptoms of PD are caused by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrement in dopamine release in the striatum. Consequently, the therapy of celltransplantation for PD consists in grafting dopamineproducing cells directly into the brain to reestablish dopamine levels. Different cell sources have been shown to induce functional benefits on both animal models of PD and human patients. However, the observed motor improvements are highly variable between individual subjects, and the sources of this variability are not fully understood. The purpose of this review is to provide a general overview of the pioneering studies done in animal models of PD that established the basis for the first clinical trials in humans, and compare these with the latest findings to identify the most relevant aspects that remain unanswered to date. The main focus of the discussions presented here will be on the mechanisms associated with the survival and functionality of the transplants. These include the role of the dopamine released by the grafts and the capacity of the grafted cells to extend fibers and to integrate into the motor circuit. The complete understanding of these aspects will require extensive research on basic aspects of molecular and cellular physiology, together with neuronal network function, in order to uncover the real potential of cell grafting for treating PD.
文摘Parkinson’s disease (PD) or Paralysis Agitans was first formally described in “An essay on the shaking palsy”, published in 1817 by a British physician named James Parkinson. In the late 1950’s, dopamine was related with the function of the corpus striatum, thus with the control of motor function. But it was not until 1967, when the landmark study of George C. Cotzias, demonstrated that oral L-DOPA, the precursor of dopamine metabolism, was shown to induce remission of PD symptoms, that the definitive association between the two was firmly established. However, later on L-DOPA treatment began to show a loss of effectiveness and demonstrated to induce a variety of undesirable effects, the most prominent being diskinesia. As a result of this, a variety of alternative or complementary pharmacological strategies have been developed. In this chapter we review the wide variety of strategies that have been used through time, which are geared toward reducing the most disabling symptoms of PD. We additionally make some suggestions as to which are the most promising ones.
