Abstract
Parkinson’s disease (PD) is the second-leading cause of dementia and is characterized by a progressive loss of dopaminergic neurons in the substantia nigra alongside the presence of intraneuronal α-synuclein-positive inclusions. Therapies to date have been directed to the restoration of the dopaminergic system, and the prevention of dopaminergic neuronal cell death in the midbrain. This review discusses the physiological mechanisms involved in PD as well as new and prospective therapies for the disease. The current data suggest that prevention or early treatment of PD may be the most effective therapeutic strategy. New advances in the understanding of the underlying mechanisms of PD predict the development of more personalized and integral therapies in the years to come. Thus, the development of more reliable biomarkers at asymptomatic stages of the disease, and the use of genetic profiling of patients will surely permit a more effective treatment of PD.
Highlights
Due to the inability to find effective preventive or curative therapies (Fox et al, 2018), epidemiological predictions for the worldwide incidence of Parkinson’s disease (PD) are not optimistic (Lees et al, 2009; AlDakheel et al, 2014; Savica et al, 2016)
We review the pathological changes associated with the functional disorganization of the frontostriatal circuit in PD and overview current efforts to develop therapeutic approaches for treating PD
Simultaneous glutamatergic projections from the prefrontal cortex (PFC) and premotor cortex (PrC) to the striatum are subjected to conditional modulation via substantia nigra pars compacta (SNc) DA, which in turn projects via the direct and indirect pathways that loop back to the PrC and primary motor cortices by way of interface nuclei of the basal ganglia and, the thalamus
Summary
Reviewed by: Guoxiang Liu, Northwestern University, United States Shane V. Boston Children’s Hospital and Harvard Medical School, United States. Therapies to date have been directed to the restoration of the dopaminergic system, and the prevention of dopaminergic neuronal cell death in the midbrain. This review discusses the physiological mechanisms involved in PD as well as new and prospective therapies for the disease. The current data suggest that prevention or early treatment of PD may be the most effective therapeutic strategy. New advances in the understanding of the underlying mechanisms of PD predict the development of more personalized and integral therapies in the years to come. The development of more reliable biomarkers at asymptomatic stages of the disease, and the use of genetic profiling of patients will surely permit a more effective treatment of PD
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