Adeno-associated virus vector as a platform for gene therapy delivery

Nature Reviews Drug Discovery, Год журнала: 2019, Номер 18(5), С. 358 - 378

Опубликована: Фев. 1, 2019

Язык: Английский

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Blood-Brain Barrier: From Physiology to Disease and Back

Physiological Reviews, Год журнала: 2018, Номер 99(1), С. 21 - 78

Опубликована: Окт. 3, 2018

The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At same time, BBB regulates transport of molecules into out central nervous system (CNS), which maintains tightly controlled chemical composition neuronal milieu that is required for proper functioning. In this review, we first examine molecular cellular mechanisms underlying establishment BBB. Then, focus on physiology, endothelial pericyte transporters, perivascular paravascular transport. Next, discuss rare human monogenic neurological disorders with primary genetic defect in BBB-associated cells demonstrating link between breakdown neurodegeneration. review effects genes inheritance and/or increased susceptibility Alzheimer's disease (AD), Parkinson's (PD), Huntington's disease, amyotrophic lateral sclerosis (ALS) relation to other pathologies deficits. We next how dysfunction relates deficits majority sporadic AD, PD, ALS cases, multiple sclerosis, neurodegenerative disorders, acute CNS such as stroke, traumatic brain injury, spinal cord epilepsy. Lastly, BBB-based therapeutic opportunities. conclude lessons learned future directions, emphasis technological advances investigate functions living brain, at level, address key unanswered questions.

Язык: Английский

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Engineering adeno-associated virus vectors for gene therapy

Nature Reviews Genetics, Год журнала: 2020, Номер 21(4), С. 255 - 272

Опубликована: Фев. 10, 2020

Язык: Английский

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A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

Cell, Год журнала: 2021, Номер 184(12), С. 3222 - 3241.e26

Опубликована: Май 17, 2021

Язык: Английский

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Comparative cellular analysis of motor cortex in human, marmoset and mouse

Nature, Год журнала: 2021, Номер 598(7879), С. 111 - 119

Опубликована: Окт. 6, 2021

Abstract The primary motor cortex (M1) is essential for voluntary fine-motor control and functionally conserved across mammals 1 . Here, using high-throughput transcriptomic epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys mice, we demonstrate a broadly cellular makeup this region, with similarities that mirror evolutionary distance are consistent between the transcriptome epigenome. core molecular identities neuronal non-neuronal cell types allow us to generate cross-species consensus classification types, infer properties species. Despite overall conservation, however, many species-dependent specializations apparent, including differences cell-type proportions, gene expression, DNA methylation chromatin state. Few marker genes species, revealing short list candidate regulatory mechanisms responsible features homologous such as GABAergic chandelier cells. This allows use patch–seq (a combination whole-cell patch-clamp recordings, RNA sequencing morphological characterization) identify corticospinal Betz cells from layer 5 non-human primates characterize their highly specialized physiology anatomy. These findings highlight robust underpinnings diversity M1 mammals, point pathways functional identity species-specific adaptations.

Язык: Английский

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Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution

Cell, Год журнала: 2020, Номер 182(6), С. 1623 - 1640.e34

Опубликована: Сен. 1, 2020

Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic translational research. We developed light-sensitive human retinal with multiple nuclear synaptic layers functional synapses. sequenced RNA 285,441 single cells from these at seven developmental time points periphery, fovea, pigment epithelium choroid light-responsive adult retinas, performed histochemistry. Cell types in matured vitro to a stable "developed" state rate similar retina development vivo. Transcriptomes organoid cell converged toward transcriptomes peripheral types. Expression disease-associated genes was cell-type-specific retina, specificity retained organoids. implicate unexpected diseases such as macular degeneration. This resource identifies cellular targets studying disease mechanisms targeted repair retinas.

Язык: Английский

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Tissue clearing and its applications in neuroscience

Nature reviews. Neuroscience, Год журнала: 2020, Номер 21(2), С. 61 - 79

Опубликована: Янв. 2, 2020

Язык: Английский

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Reconstruction of 1,000 Projection Neurons Reveals New Cell Types and Organization of Long-Range Connectivity in the Mouse Brain

Cell, Год журнала: 2019, Номер 179(1), С. 268 - 281.e13

Опубликована: Сен. 1, 2019

Язык: Английский

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The blood-brain barrier: Physiology and strategies for drug delivery

Advanced Drug Delivery Reviews, Год журнала: 2019, Номер 165-166, С. 1 - 14

Опубликована: Ноя. 29, 2019

Язык: Английский

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LRP1 is a master regulator of tau uptake and spread

Nature, Год журнала: 2020, Номер 580(7803), С. 381 - 385

Опубликована: Апрель 1, 2020

Язык: Английский

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