Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, characterized by resting tremor, rigidity, and bradykinesia. Striatal dopamine deficiency caused by the loss of nigral dopaminergic neurons is the main pathological feature of PD. Midbrain dopaminergic neurons are split into two major populations, the substantia nigra compacta (SNc) and the ventral tegmental area (VTA). SNc dopamine neurons are severely affected in PD whilst VTA neurons are more resilient to neurodegeneration. Understanding the factors that contribute to dopaminergic cell death are essential to identifying new drug targets and developing disease-modifying agents.
The objective of this Research Topic is to explore the factors that contribute to dopaminergic cell death. For example, defining the transcriptional profiles as well as the energy demands of SNc and VTA neurons is crucial to understanding the mechanisms underlying the differences in their vulnerability to neurodegeneration. Furthermore, specific investigation of the pathways that affect dopaminergic neuron cell death is vital to identify potential therapeutic targets. For example, dysregulation of glycogen synthase kinase-3 beta (GSK-3ß) has been directly implicated in nigral dopaminergic neurodegeneration. Moreover, metformin, a first-line drug for the treatment of type II diabetes, appears to have a neuroprotective effect on dopaminergic neurons that is mediated by the activation of AMPK-FOXO3 signaling and the inhibition of the proangiogenic factor VEGF; however, other studies have shown hazardous effects of metformin on the dopaminergic SNc system. These examples suggest that in studying the causes of dopaminergic neurodegeneration in PD, we are dealing with a complex and multifactorial system in which different mechanisms of neuronal death coexist, which in turn are triggered and influenced by different factors, ranging from purely genetic to purely environmental.
Themes included in this Research Topic include, but are not limited to:
1. Exploration of signaling pathways linked to dopaminergic cell death and to the vulnerability of dopaminergic neurons to neurodegeneration.
2. The potential role of microglia and astroglia in the induction of neuroinflammation in Parkinson's disease and their influence on dopaminergic neuron survival.
3. Investigation into the role of the Lewy pathology/Lewy bodies as a causative or protective element in dopaminergic cell death.
4. The identification of new potential therapeutic targets and early predictive markers of the disease. Finding these early markers, combined with knowledge of the mechanisms of neuronal death, may be the key to preventing the development of this disease.
Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, characterized by resting tremor, rigidity, and bradykinesia. Striatal dopamine deficiency caused by the loss of nigral dopaminergic neurons is the main pathological feature of PD. Midbrain dopaminergic neurons are split into two major populations, the substantia nigra compacta (SNc) and the ventral tegmental area (VTA). SNc dopamine neurons are severely affected in PD whilst VTA neurons are more resilient to neurodegeneration. Understanding the factors that contribute to dopaminergic cell death are essential to identifying new drug targets and developing disease-modifying agents.
The objective of this Research Topic is to explore the factors that contribute to dopaminergic cell death. For example, defining the transcriptional profiles as well as the energy demands of SNc and VTA neurons is crucial to understanding the mechanisms underlying the differences in their vulnerability to neurodegeneration. Furthermore, specific investigation of the pathways that affect dopaminergic neuron cell death is vital to identify potential therapeutic targets. For example, dysregulation of glycogen synthase kinase-3 beta (GSK-3ß) has been directly implicated in nigral dopaminergic neurodegeneration. Moreover, metformin, a first-line drug for the treatment of type II diabetes, appears to have a neuroprotective effect on dopaminergic neurons that is mediated by the activation of AMPK-FOXO3 signaling and the inhibition of the proangiogenic factor VEGF; however, other studies have shown hazardous effects of metformin on the dopaminergic SNc system. These examples suggest that in studying the causes of dopaminergic neurodegeneration in PD, we are dealing with a complex and multifactorial system in which different mechanisms of neuronal death coexist, which in turn are triggered and influenced by different factors, ranging from purely genetic to purely environmental.
Themes included in this Research Topic include, but are not limited to:
1. Exploration of signaling pathways linked to dopaminergic cell death and to the vulnerability of dopaminergic neurons to neurodegeneration.
2. The potential role of microglia and astroglia in the induction of neuroinflammation in Parkinson's disease and their influence on dopaminergic neuron survival.
3. Investigation into the role of the Lewy pathology/Lewy bodies as a causative or protective element in dopaminergic cell death.
4. The identification of new potential therapeutic targets and early predictive markers of the disease. Finding these early markers, combined with knowledge of the mechanisms of neuronal death, may be the key to preventing the development of this disease.