Treating Parkinson’s disease by astrocyte reprogramming: Progress and challenges

Wei, Zhuang‐Yao D.; Shetty, Ashok K.

doi:10.1126/sciadv.abg3198

Cited by 28 publications

(25 citation statements)

References 76 publications

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“…Second, astrocytes aid in the maintenance of blood brain barrier (BBB) homeostasis. Astrocytes maintain a portion of their protective effect on BBB integrity by secreting anti-inflammatory factors such as sonic hedgehog, angiopoietin-1, retinoic acid, and insulin-like growth factor-1 to anti-inflammation, and prostaglandins, nitric oxide, or arachidonic acid to regulate cerebrovascular flow (Wei and Shetty, 2021;Zhao et al, 2021).…”

Section: The Basic Role Of Astrocytes In Neurodegenerationmentioning

confidence: 99%

Astrocytes in Neurodegeneration: Inspiration From Genetics

Huang

Shang

2022

Front. Neurosci.

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Despite the discovery of numerous molecules and pathologies, the pathophysiology of various neurodegenerative diseases remains unknown. Genetics participates in the pathogenesis of neurodegeneration. Neural dysfunction, which is thought to be a cell-autonomous mechanism, is insufficient to explain the development of neurodegenerative disease, implying that other cells surrounding or related to neurons, such as glial cells, are involved in the pathogenesis. As the primary component of glial cells, astrocytes play a variety of roles in the maintenance of physiological functions in neurons and other glial cells. The pathophysiology of neurodegeneration is also influenced by reactive astrogliosis in response to central nervous system (CNS) injuries. Furthermore, those risk-gene variants identified in neurodegenerations are involved in astrocyte activation and senescence. In this review, we summarized the relationships between gene variants and astrocytes in four neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson’s disease (PD), and provided insights into the implications of astrocytes in the neurodegenerations.

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Section: The Basic Role Of Astrocytes In Neurodegenerationmentioning

confidence: 99%

Astrocytes in Neurodegeneration: Inspiration From Genetics

Huang

Shang

2022

Front. Neurosci.

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“…The latter two nuclei showed MD2 dopaminergic neurons projecting to the striatum. These dopaminergic projections are well known for their involvement in regulating movement and sabotaged in Parkinson's disease [49]. This raises the question of what physiological roles MD2 play in movement control of the body, eyes, and the face.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical localization of MD2, a co-receptor of TLR4, in the adult mouse brain

Liang

Dong

et al. 2022

Preprint

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Background: MD2, a co-receptor of a classical proinflammatory protein TLR4 whose activation leads to neuroinflammation. It is widely accepted that TLR4 is expressed on the cell surface of microglia and astrocytes, and MD2 is expected to be expressed by these cells as well. However, our previous study showed that neurons from certain nuclei also expressed MD2. Whether MD2 is expressed by other brain nuclei is still unknown. It is the aim of the present study to map the distribution of MD2 positive cells in the adult mouse brain.Methods: Immunohistochemical staining against MD2 was completed to localize MD2 positive cells in the mouse brain by comparing the location of positive cells with the mouse brain atlas. Retrograde tracing and double immunofluorescence staining with both MD2 and TH were conducted to examine whether dopaminergic neurons in the substantia nigra projecting to the striatum were MD2 positive.Results: MD2 positive cells were found in the majority of mouse brain nuclei with clusters of cells in the olfactory bulb, cortices, the red nucleus, and cranial nuclei. Subcortical nuclei had heterogenous staining of MD2 with more prominent cells in the basolateral and the central amygdaloid nuclei. The ventral pallidum and the diagonal bands had positive cells with similar density and shape. Prominent cells were present in thalamic nuclei which were nearly homogenous, reticular formation of the brainstem where cells were dispersed with similar density. The hypothalamus had fewer outstanding cells compared with the thalamus. The red nucleus, the substantia nigra, and the ventral tegmental area in the pretectum had outstanding cells with the latter two containing dopaminergic neurons projecting to the striatum as shown in retrograde tracing and double fluorescence staining. Raphe, sensory cranial, and deep cerebellar nuclei also had MD2 positive cells with moderate density.Conclusion: MD2 is present not only in glial cells, but also in neurons. Some MD2 positive dopaminergic neurons in SNC and VTA projected to the striatum.

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“…The latter approach has attracted a lot of attention in recent years because the direct reprogramming of adult post-mitotic cells might be quite useful in the replacement of lost neurons with new cells in brain regions (i.e., SN and striatum) with very limited neurogenic capacity in adults [242]. However, the conversion of SN GFAP + cells into neurons was found, thereby providing an alternative neurogenic mechanism within SN and striatum: GFAP + /s100β + astrocytes could transdifferentiate into dividing cells (neuroblasts) or even dedifferentiate back to NSCs [64].…”

Section: Alternative Approaches To Restoring Impaired Neurogenesis In Pdmentioning

confidence: 99%

Novel Approaches Used to Examine and Control Neurogenesis in Parkinson′s Disease

Салмина

Kapkaeva

Ветчинова

et al. 2021

IJMS

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Neurogenesis is a key mechanism of brain development and plasticity, which is impaired in chronic neurodegeneration, including Parkinson’s disease. The accumulation of aberrant α-synuclein is one of the features of PD. Being secreted, this protein produces a prominent neurotoxic effect, alters synaptic plasticity, deregulates intercellular communication, and supports the development of neuroinflammation, thereby providing propagation of pathological events leading to the establishment of a PD-specific phenotype. Multidirectional and ambiguous effects of α-synuclein on adult neurogenesis suggest that impaired neurogenesis should be considered as a target for the prevention of cell loss and restoration of neurological functions. Thus, stimulation of endogenous neurogenesis or cell-replacement therapy with stem cell-derived differentiated neurons raises new hopes for the development of effective and safe technologies for treating PD neurodegeneration. Given the rapid development of optogenetics, it is not surprising that this method has already been repeatedly tested in manipulating neurogenesis in vivo and in vitro via targeting stem or progenitor cells. However, niche astrocytes could also serve as promising candidates for controlling neuronal differentiation and improving the functional integration of newly formed neurons within the brain tissue. In this review, we mainly focus on current approaches to assess neurogenesis and prospects in the application of optogenetic protocols to restore the neurogenesis in Parkinson’s disease.

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Treating Parkinson’s disease by astrocyte reprogramming: Progress and challenges

Cited by 28 publications

References 76 publications

Astrocytes in Neurodegeneration: Inspiration From Genetics

Astrocytes in Neurodegeneration: Inspiration From Genetics

Immunohistochemical localization of MD2, a co-receptor of TLR4, in the adult mouse brain

Novel Approaches Used to Examine and Control Neurogenesis in Parkinson′s Disease

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