Engrafted primary type-2 astrocytes improve the recovery of the nigrostriatal pathway in a rat model of Parkinson's disease

Sun, Yuanheng; Lu, Xiaojun; Fu, Xinghui; Zhang, Ye; Zhan, Yan; Liu, Jiabing; Zhao, Liang; Xia, Chunlin

doi:10.1007/s11010-020-03931-3

Cited by 4 publications

(5 citation statements)

References 37 publications

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“…FEZ1 abnormalities have been previously linked to Alzheimer’s and Parkinson’s disease as well as ADHD and SCZ-like behavior in FEZ1 knockout mice and in Jacobsen syndrome (JS) patients. 9 , 17 , 18 , 21 , 40 Additionally, genes associated with depression and intellectual disability were highly represented in FEZ1-null hCOs. Collectively, these results indicated FEZ1’s involvement in early human brain development and that loss of FEZ1 potentially triggers changes in biological pathways contributing to neurodevelopmental as well as neurodegenerative disorders.…”

Section: Resultsmentioning

confidence: 98%

FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migrations

Qu,

Lim,

et al. 2023

iScience

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Section: Resultsmentioning

confidence: 98%

FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migrations

Qu,

Lim,

et al. 2023

iScience

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“…2F). FEZ1 abnormalities have been previously linked to Alzheimer’s and Parkinson’s disease as well as schizophrenia and ADHD (Butkevich et al, 2016; Sakae et al, 2008; Sumitomo et al, 2018; Sun et al, 2020). Additionally, genes associated with depression and intellectual disability were highly represented in FEZ1-null hCOs.…”

Section: Resultsmentioning

confidence: 99%

“…2F). FEZ1 abnormalities have been previously linked to Alzheimer's and Parkinson's disease as well as schizophrenia and ADHD (Butkevich et al, 2016;Sakae et al, 2008;Sumitomo et al, 2018;Sun et al, 2020).…”

Section: Loss Of Fez1 Alters Expression Of Genes Involved In Early Br...mentioning

confidence: 99%

FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migration

Yang

et al. 2022

Preprint

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Abnormal neuronal networks arising from perturbations during early brain development contribute to neurodevelopmental disorders. Mutations and deletions of human Fasciculation and Elongation Protein Zeta 1 (FEZ1) are found in schizophrenia and Jacobsen syndrome patients. However, its roles in human brain development and manifestation of clinical pathological symptoms remain unknown. Here, using human cerebral organoids (hCOs), we observed that FEZ1 expression is turned on early during brain development and is detectable in both neuroprogenitor subtypes and immature neurons. Deletion of FEZ1 disrupts expression of genes involved in neuronal and synaptic development. Using single-cell RNA sequencing, we further uncovered an abnormal expansion of homeodomain-only protein homeobox (HOPX)- outer radial glia (oRG) in FEZ1-null hCOs, occurring at the expense of HOPX+ oRG. HOPX- oRGs show higher cell mobility as compared to HOPX+ oRGs, which is accompanied by the ectopic localization of the neuroprogenitors to the outer layer of FEZ1-null hCOs. Moreover, abnormal encroachment of TBR2+ intermediate progenitors into CTIP2+ deep layer neurons indicated that cortical layer formation is disrupted in FEZ1-null hCOs. Collectively, our findings highlight the involvement of FEZ1 in early cortical brain development and how it contributes to neurodevelopmental disorders.

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“…This switches the neurorescue-unfriendly environment of SN to a beneficial antioxidant/anti-inflammatory prosurvival milieu [ 170 ]. Similarly, engrafted type-2 astrocytes, a specific type of neonatal astrocytes with some characteristics of neural stem cells, have been used to repair the nigrostriatal pathway, improve symptoms, and induce functional reconstruction in 6-OHDA-induced PD rats [ 171 ]. Using single-cell RNA sequencing combined with comprehensive histological analyses, researchers have found that along with neurons, astrocytes are also a major component of both fetal and stem cell-derived intracerebral grafts after functional maturation, indicating a new source of functional astrocytes for transplantation [ 172 ].…”

Section: Replenishment Of Functional Astrocytesmentioning

confidence: 99%

Astrocyte dysfunction in Parkinson's disease: from the perspectives of transmitted α-synuclein and genetic modulation

Wang

Yang

Liang

et al. 2021

Transl Neurodegener

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Parkinson’s disease (PD) is a common neurodegenerative disorder that primarily affects the elderly. While the etiology of PD is likely multifactorial with the involvement of genetic, environmental, aging and other factors, α-synuclein (α-syn) pathology is a pivotal mechanism underlying the development of PD. In recent years, astrocytes have attracted considerable attention in the field. Although astrocytes perform a variety of physiological functions in the brain, they are pivotal mediators of α-syn toxicity since they internalize α-syn released from damaged neurons, and this triggers an inflammatory response, protein degradation dysfunction, mitochondrial dysfunction and endoplasmic reticulum stress. Astrocytes are indispensable coordinators in the background of several genetic mutations, including PARK7, GBA1, LRRK2, ATP13A2, PINK1, PRKN and PLA2G6. As the most abundant glial cells in the brain, functional astrocytes can be replenished and even converted to functional neurons. In this review, we discuss astrocyte dysfunction in PD with an emphasis on α-syn toxicity and genetic modulation and conclude that astrocyte replenishment is a valuable therapeutic approach in PD.

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Engrafted primary type-2 astrocytes improve the recovery of the nigrostriatal pathway in a rat model of Parkinson's disease

Cited by 4 publications

References 37 publications

FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migrations

FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migrations

FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migration

Astrocyte dysfunction in Parkinson's disease: from the perspectives of transmitted α-synuclein and genetic modulation

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