Bioinformatic analysis of the human brain extracellular matrix proteome in neurodegenerative disorders

2021 ◽  
Author(s):  
Ana Freitas ◽  
Miguel Aroso ◽  
Sara Rocha ◽  
Rita Ferreira ◽  
Rui Vitorino ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Human Brain ◽  
Neurodegenerative Disorders ◽  
Bioinformatic Analysis ◽  
Brain Extracellular Matrix

scholarly journals Identification of variable lymphocyte receptors that can target therapeutics to pathologically exposed brain extracellular matrix

2019 ◽  
Vol 5 (5) ◽  
pp. eaau4245 ◽  
Author(s):  
Benjamin J. Umlauf ◽  
Paul A. Clark ◽  
Jason M. Lajoie ◽  
Julia V. Georgieva ◽  
Samantha Bremner ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Human Brain ◽  
Surface Display ◽  
Yeast Surface Display ◽  
Blood Components ◽  
Human Brain Tissue ◽  
Tissue Sections ◽  
Yeast Surface ◽  
Lymphocyte Receptors ◽  
Brain Extracellular Matrix

Diseases that lead to blood-brain barrier (BBB) disruption will pathologically expose normally inaccessible brain extracellular matrix (ECM) to circulating blood components. Therefore, we hypothesized that brain ECM-targeting moieties could specifically target the disrupted BBB and potentially deliver therapies. Variable lymphocyte receptors (VLRs) that preferentially associate with brain ECM were identified from an immune VLR library via yeast surface display biopanning coupled with a moderate throughput ECM screen. Brain ECM binding of VLR clones to murine and human brain tissue sections was confirmed. After systemic administration, P1C10, the lead brain ECM-targeting VLR candidate, specifically accumulated in brains with mannitol-disrupted BBB and at disrupted BBB regions in two different intracranial glioblastoma models. We also demonstrate P1C10’s ability to deliver doxorubicin-loaded liposomes, leading to significantly improved survival in glioblastoma-bearing mice. Thus, VLRs can be used to selectively target pathologically exposed brain ECM and deliver drug payloads.

scholarly journals Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ann-Na Cho ◽  
Yoonhee Jin ◽  
Yeonjoo An ◽  
Jin Kim ◽  
Yi Sun Choi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Human Brain ◽  
Microfluidic Device ◽  
Pluripotent Stem Cells ◽  
Brain Diseases ◽  
Organoid Culture ◽  
Brain Organoid ◽  
Brain Extracellular Matrix

AbstractBrain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.

scholarly journals A brain extracellular matrix proteoglycan forms aggregates with hyaluronan

1993 ◽  
Vol 268 (20) ◽  
pp. 15061-15069
Author(s):  
M. Iwata ◽  
T.N. Wight ◽  
S.S. Carlson
Keyword(s):  
Extracellular Matrix ◽  
Brain Extracellular Matrix

scholarly journals Deubiquitylating enzymes in neuronal health and disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fatima Amer-Sarsour ◽  
Alina Kordonsky ◽  
Yevgeny Berdichevsky ◽  
Gali Prag ◽  
Avraham Ashkenazi
Keyword(s):  
Human Brain ◽  
Neurodegenerative Disorders ◽  
Structure And Function ◽  
Pivotal Role ◽  
Protein Homeostasis ◽  
Neuronal Function ◽  
Health And Disease ◽  
And Function

AbstractUbiquitylation and deubiquitylation play a pivotal role in protein homeostasis (proteostasis). Proteostasis shapes the proteome landscape in the human brain and its impairment is linked to neurodevelopmental and neurodegenerative disorders. Here we discuss the emerging roles of deubiquitylating enzymes in neuronal function and survival. We provide an updated perspective on the genetics, physiology, structure, and function of deubiquitylases in neuronal health and disease.

scholarly journals Multiple Particle Tracking Detects Changes in Brain Extracellular Matrix and Predicts Neurodevelopmental Age

ACS Nano ◽  
2021 ◽  
Author(s):  
Michael McKenna ◽  
David Shackelford ◽  
Hugo Ferreira Pontes ◽  
Brendan Ball ◽  
Elizabeth Nance
Keyword(s):  
Extracellular Matrix ◽  
Particle Tracking ◽  
Multiple Particle Tracking ◽  
Multiple Particle ◽  
Brain Extracellular Matrix

scholarly journals Enzymatic Digestion of Hyaluronan-Based Brain Extracellular Matrix in vivo Can Induce Seizures in Neonatal Mice

2019 ◽  
Vol 13 ◽  
Author(s):  
Alena Balashova ◽  
Vladimir Pershin ◽  
Olga Zaborskaya ◽  
Natalia Tkachenko ◽  
Andrey Mironov ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Enzymatic Digestion ◽  
Neonatal Mice ◽  
Brain Extracellular Matrix
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