AI Article Synopsis
- The CRISPR-Cas9 genome editing system is utilized to create mutations in specific genes, leading to the loss of functional proteins.
- A transgenic zebrafish model for α1-antitrypsin deficiency (AATD) exhibits a unique phenotype, lacking the typical liver accumulation of misfolded protein seen in humans and mice.
- The study highlights the use of CRISPR-Cas9 to create mutant zebrafish targeting the atf6a and man1b1 genes, which are suspected to play a role in processing misfolded α1-antitrypsin in the liver.
Article Abstract
The CRISPR-Cas9 genome editing system is used to induce mutations in genes of interest resulting in the loss of functional protein. A transgenic zebrafish α1-antitrypsin deficiency (AATD) model displays an unusual phenotype, in that it lacks the hepatic accumulation of the misfolding Z α1-antitrypsin (ZAAT) evident in human and mouse models. Here we describe the application of the CRISPR-Cas9 system to generate mutant zebrafish with defects in key proteostasis networks likely to be involved in the hepatic processing of ZAAT in this model. We describe the targeting of the atf6a and man1b1 genes as examples.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/978-1-0716-3605-3_3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Impairment of lipid homeostasis causes lysosomal accumulation of endogenous protein aggregates through ESCRT disruption.
Elife
December 2024
Calico Life Sciences LLC, South San Francisco, United States.
Protein aggregation increases during aging and is a pathological hallmark of many age-related diseases. Protein homeostasis (proteostasis) depends on a core network of factors directly influencing protein production, folding, trafficking, and degradation. Cellular proteostasis also depends on the overall composition of the proteome and numerous environmental variables.
View Article and Find Full Text PDFAutophagy induction by piplartine ameliorates axonal degeneration caused by mutant HSPB1 and HSPB8 in charcot-marie-tooth type 2 neuropathies.
Autophagy
December 2024
Peripheral Neuropathy Research Group, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
HSPB1 [heat shock protein family B (small) member 1] and HSPB8 are essential molecular chaperones for neuronal proteostasis, as they prevent protein aggregation. Mutant HSPB1 and HSPB8 primarily harm peripheral neurons, resulting in axonal Charcot-Marie-Tooth neuropathies (CMT2). Macroautophagy/autophagy is a shared mechanism by which HSPB1 and HSPB8 mutations cause neuronal dysfunction.
View Article and Find Full Text PDFAutophagy and Protein Quality Control in Parkinson's Disease.
Cold Spring Harb Perspect Med
December 2024
Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute (VHIR) Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 08035 Barcelona, Spain.
Autophagy is a vital cellular process responsible for the degradation of proteins, organelles, and other cellular components within lysosomes. In neurons, basal autophagy is indispensable for maintaining cellular homeostasis and protein quality control. Accordingly, lysosomal dysfunction has been proposed to be associated with neurodegeneration, and with Parkinson's disease (PD) in particular.
View Article and Find Full Text PDFChaperone-mediated autophagy as a modulator of aging and longevity.
Front Aging
December 2024
Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM, United States.
Chaperone-mediated autophagy (CMA) is the lysosomal degradation of individually selected proteins, independent of vesicle fusion. CMA is a central part of the proteostasis network in vertebrate cells. However, CMA is also a negative regulator of anabolism, and it degrades enzymes required for glycolysis, lipogenesis, and translation at the cytoplasmic ribosome.
View Article and Find Full Text PDFTemporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways.
Proc Natl Acad Sci U S A
December 2024
Department of Cell Biology, Harvard Medical School, Boston MA 02115.
A hallmark of neurodegenerative diseases (NDs) is the progressive loss of proteostasis, leading to the accumulation of misfolded proteins or protein aggregates, with subsequent cytotoxicity. To combat this toxicity, cells have evolved degradation pathways (ubiquitin-proteasome system and autophagy) that detect and degrade misfolded proteins. However, studying the underlying cellular pathways and mechanisms has remained a challenge, as formation of many types of protein aggregates is asynchronous, with individual cells displaying distinct kinetics, thereby hindering rigorous time-course studies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!