About this Research Topic
Parkinson’s disease (PD) is a complex neurodegenerative disorder affecting over 1% of the elderly population and represents an increasing socioeconomic burden in our aging society.
Over the past two decades, we witnessed a tremendous growth in our understanding of the pathophysiology and the phenomenology of PD. Advancements in genetic and biochemistry have led to the identification of numerous genes implicated in both familial and sporadic forms of PD. Studying the encoded mutated proteins and the pathways in which they are involved has revealed a number of shared mechanisms underlying PD pathogenesis, such as mitochondrial dysfunction, abnormal handling of misfolded proteins, oxidative stress, and lysosomal dysfunction. These findings have led to an expansion of animal models, ranging from classic neurotoxic models to newer genetic models of the disease.
Emerging preclinical and clinical evidence now support the idea that dopamine-independent mechanisms contribute to the disease pathogenesis and the phenotypic heterogeneity seen in PD patients. In addition, the pathology in PD is not restricted to the basal ganglia circuitry; rather, it is distributed and can retrogradely spread from the periphery to the substantia nigra, through synaptically coupled networks. Thus, because of complex genetic, epigenetic, and biological factors, PD is a complex and heterogenous disorder with a wide range of clinical phenotypes, responses to treatments, and survival.
However, the cross-link between clinical and preclinical research has thus far been limited, in part due to the inability of current models to completely recapitulate key behavioral and pathological phenotypes of PD. Technical advancements and mechanistic studies are still needed to overcome the limitations of available treatments and improve the development of biomarkers, the success of disease-modifying therapies and the understanding of the relationship between pathogenic mechanisms and clinical symptoms.
Therefore, the main purpose of this Research Topic is to encourage cross-talk between preclinical and clinical research to improve the current models used to study the pathogenesis and the phenomenology of PD. We welcome contributions in the form of original research papers, review articles, technical reports and commentaries focusing on the study of preclinical and clinical models of PD using single or multiple experimental approaches. Researchers involved in developing preclinical models, whose main goal is to recapitulate the key phenotypic and neuropathological features of PD, are encouraged to submit their contributions. We seek studies using models of the multiple hit hypothesis, the prion-like transmissibility of α-synuclein related pathology, and the early perturbations in circuitry and neuronal functions. Researchers involved in clinical studies using neurophysiological (transcranial magnetic stimulation, TMS) and neuroimaging (both functional and structural MRI approaches) tools are also encouraged to contribute to this Research Topic. Close attention will be paid to studies aimed at defining a working model of network dysfunction of PD.
Over the past two decades, we witnessed a tremendous growth in our understanding of the pathophysiology and the phenomenology of PD. Advancements in genetic and biochemistry have led to the identification of numerous genes implicated in both familial and sporadic forms of PD. Studying the encoded mutated proteins and the pathways in which they are involved has revealed a number of shared mechanisms underlying PD pathogenesis, such as mitochondrial dysfunction, abnormal handling of misfolded proteins, oxidative stress, and lysosomal dysfunction. These findings have led to an expansion of animal models, ranging from classic neurotoxic models to newer genetic models of the disease.
Emerging preclinical and clinical evidence now support the idea that dopamine-independent mechanisms contribute to the disease pathogenesis and the phenotypic heterogeneity seen in PD patients. In addition, the pathology in PD is not restricted to the basal ganglia circuitry; rather, it is distributed and can retrogradely spread from the periphery to the substantia nigra, through synaptically coupled networks. Thus, because of complex genetic, epigenetic, and biological factors, PD is a complex and heterogenous disorder with a wide range of clinical phenotypes, responses to treatments, and survival.
However, the cross-link between clinical and preclinical research has thus far been limited, in part due to the inability of current models to completely recapitulate key behavioral and pathological phenotypes of PD. Technical advancements and mechanistic studies are still needed to overcome the limitations of available treatments and improve the development of biomarkers, the success of disease-modifying therapies and the understanding of the relationship between pathogenic mechanisms and clinical symptoms.
Therefore, the main purpose of this Research Topic is to encourage cross-talk between preclinical and clinical research to improve the current models used to study the pathogenesis and the phenomenology of PD. We welcome contributions in the form of original research papers, review articles, technical reports and commentaries focusing on the study of preclinical and clinical models of PD using single or multiple experimental approaches. Researchers involved in developing preclinical models, whose main goal is to recapitulate the key phenotypic and neuropathological features of PD, are encouraged to submit their contributions. We seek studies using models of the multiple hit hypothesis, the prion-like transmissibility of α-synuclein related pathology, and the early perturbations in circuitry and neuronal functions. Researchers involved in clinical studies using neurophysiological (transcranial magnetic stimulation, TMS) and neuroimaging (both functional and structural MRI approaches) tools are also encouraged to contribute to this Research Topic. Close attention will be paid to studies aimed at defining a working model of network dysfunction of PD.
Keywords: Parkinson's disease, preclinical model, dopamine, synuclein, neural network
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