Neuron-Astrocyte Interactions in Parkinson’s Disease

Miyazaki, Ikuko; Asanuma, Masato

doi:10.3390/cells9122623

Cited by 104 publications

(81 citation statements)

References 244 publications

(297 reference statements)

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“…In these diseases, chronic exposure to ROS and dysregulated signaling between astrocytes, CNS endothelial cells, and pericytes cause the barriers to become hyperpermeable, allowing the invasion of monocytes and other peripheral immune cells into the CNS ( 65 , 66 ). In Parkinson’s disease (PD), increased BBB permeability may be attributed to α-synuclein-induced dysfunction in astrocytes ( 67 ) – the PD-associated α-synuclein (A53T) mutation has been found to cause BBB breakdown and neurodegeneration when selectively expressed by astrocytes in a mouse model ( 68 ).…”

Section: Blood-brain and Blood-cerebrospinal Fluid Barriersmentioning

confidence: 99%

Immune Response in Neurological Pathology: Emerging Role of Central and Peripheral Immune Crosstalk

et al. 2021

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Neuroinflammation is a key component of neurological disorders and is an important therapeutic target; however, immunotherapies have been largely unsuccessful. In cases where these therapies have succeeded, particularly multiple sclerosis, they have primarily focused on one aspect of the disease and leave room for improvement. More recently, the impact of the peripheral immune system is being recognized, since it has become evident that the central nervous system is not immune-privileged, as once thought. In this review, we highlight key interactions between central and peripheral immune cells in neurological disorders. While traditional approaches have examined these systems separately, the immune responses and processes in neurological disorders consist of substantial crosstalk between cells of the central and peripheral immune systems. Here, we provide an overview of major immune effector cells and the role of the blood-brain barrier in regard to neurological disorders and provide examples of this crosstalk in various disorders, including stroke and traumatic brain injury, multiple sclerosis, neurodegenerative diseases, and brain cancer. Finally, we propose targeting central-peripheral immune interactions as a potential improved therapeutic strategy to overcome failures in clinical translation.

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Section: Blood-brain and Blood-cerebrospinal Fluid Barriersmentioning

confidence: 99%

Immune Response in Neurological Pathology: Emerging Role of Central and Peripheral Immune Crosstalk

et al. 2021

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“…A1 type astrocytes represent reactive microglia-induced cells in stress or disease conditions and are induced by the release of IL-1, TNF and C1q [ 111 , 121 ]. These reactive cells are detected in injured brain regions, where they lose normal functions, release proinflammatory factors (IL-1, IL-1, and TNF), contribute to inflammatory neurodegeneration, and increase their expression of a cytoskeletal protein called Glial Fibrillary Acid Protein (GFAP) [ 121 , 131 ]. However, there are contradictory results from experiments conducted on animals or the post-mortem brains of PD patients.…”

Section: Innate Immunitymentioning

confidence: 99%

“…However, there are contradictory results from experiments conducted on animals or the post-mortem brains of PD patients. Studies on human PD tissues have displayed null or mild increases of astrocytes and/or GFAP immunoreactivity [ 131 , 132 , 133 , 134 , 135 ]. On the contrary, Parkinsonian animal models undergoing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA) treatment have exhibited dramatic astrogliosis [ 131 , 136 , 137 ].…”

Section: Innate Immunitymentioning

confidence: 99%

“…In addition, astrocytes have neurotransmitter receptors and Na + -dependent excitatory amino acid transporters, such as glutamate transporter 1 (GLT-1), excitatory amino acid transporter 2 (EAAT2), and glutamate aspartate transporter (GLAST). Furthermore, they participate in glutamate re-uptake and release, defending neurons from glutamate spill over and excitotoxicity [ 131 , 141 ]. Moreover, proinflammatory factors, secreted by microglia, affect glutamatergic signals, e.g., reducing the expression of glutamate transporters [ 131 , 142 , 143 ].…”

Section: Innate Immunitymentioning

confidence: 99%

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Alpha-Synuclein as a Prominent Actor in the Inflammatory Synaptopathy of Parkinson’s Disease

Cardinale

Calabrese

Iure

et al. 2021

IJMS

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Parkinson’s disease (PD) is considered the most common disorder of synucleinopathy, which is characterised by intracellular inclusions of aggregated and misfolded α-synuclein (α-syn) protein in various brain regions, and the loss of dopaminergic neurons. During the early prodromal phase of PD, synaptic alterations happen before cell death, which is linked to the synaptic accumulation of toxic α-syn specifically in the presynaptic terminals, affecting neurotransmitter release. The oligomers and protofibrils of α-syn are the most toxic species, and their overexpression impairs the distribution and activation of synaptic proteins, such as the SNARE complex, preventing neurotransmitter exocytosis and neuronal synaptic communication. In the last few years, the role of the immune system in PD has been increasingly considered. Microglial and astrocyte activation, the gene expression of proinflammatory factors, and the infiltration of immune cells from the periphery to the central nervous system (CNS) represent the main features of the inflammatory response. One of the actors of these processes is α-syn accumulation. In light of this, here, we provide a systematic review of PD-related α-syn and inflammation inter-players.

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“…However, an interesting thing to note is that some neurons are vulnerable to this pathologic process compared to others. It is also reported that dopaminergic neurons easily degenerate in regions with less astrocytes [52][53][54][55][56].…”

Section: Introductionmentioning

confidence: 98%

Role of neuron specific enolase as a biomarker in Parkinson’s disease

Dutta¹

2021

J Neurosci Neurol Disord

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Parkinson’s disease (PD) is thought to be the most common neurodegenerative disease with movement disorder. The key motor symptoms are rigidity, tremor, akinesis/hypokinesia/bradykinesia, and postural instability. However, in our day-to-day clinical practice we tend to see several other symptoms which may be motor or non-motor. Non-motor symptoms (NMS) are quite common and debilitating. The pathological hallmarks of PD are loss of dopaminergic neurons in the substantia nigra pars compacta (SNPc) and accumulation of unfolded or misfolded alpha-synuclein. Diagnosis of PD is difficult in the pre-motor stage. Late diagnosis renders a substantial loss of dopaminergic neurons in SNPc and spread of disease in other parts of the brain. This may manifest as either full blown symptoms requiring multiple medications or may even lead to life threatening condition due to lack of early diagnostic tools and techniques. Biomarkers are required to diagnose PD at a very early stage when prevention is possible. Hence, we see a lot of interest among researchers involved in finding a biomarker specific to the disease. Biomarkers may be clinical, image based, genetic, and biochemical. Cerebrospinal fluid (CSF) and serum markers which may correlate with disease pathophysiology are of great significance. One such molecule which recently gained a lot of attention is neuron-specific enolase (NSE). The main aim of this paper is to highlight the role of NSE in predicting neurodegeneration and neuroinflammation ultimately reflecting damage of brain cells in PD.

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Neuron-Astrocyte Interactions in Parkinson’s Disease

Cited by 104 publications

References 244 publications

Immune Response in Neurological Pathology: Emerging Role of Central and Peripheral Immune Crosstalk

Immune Response in Neurological Pathology: Emerging Role of Central and Peripheral Immune Crosstalk

Alpha-Synuclein as a Prominent Actor in the Inflammatory Synaptopathy of Parkinson’s Disease

Role of neuron specific enolase as a biomarker in Parkinson’s disease

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