| 1. |
- Bedford, Lynn, et al.
(författare)
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Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies
- 2008
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 28:33, s. 8189-98
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitin-positive intraneuronal inclusions are a consistent feature of the major human neurodegenerative diseases, suggesting that dysfunction of the ubiquitin proteasome system is central to disease etiology. Research using inhibitors of the 20S proteasome to model Parkinson's disease is controversial. We report for the first time that specifically 26S proteasomal dysfunction is sufficient to trigger neurodegenerative disease. Here, we describe novel conditional genetic mouse models using the Cre/loxP system to spatially restrict inactivation of Psmc1 (Rpt2/S4) to neurons of either the substantia nigra or forebrain (e.g., cortex, hippocampus, and striatum). PSMC1 is an essential subunit of the 26S proteasome and Psmc1 conditional knock-out mice display 26S proteasome depletion in targeted neurons, in which the 20S proteasome is not affected. Impairment of specifically ubiquitin-mediated protein degradation caused intraneuronal Lewy-like inclusions and extensive neurodegeneration in the nigrostriatal pathway and forebrain regions. Ubiquitin and alpha-synuclein neuropathology was evident, similar to human Lewy bodies, but interestingly, inclusion bodies contained mitochondria. We support this observation by demonstrating mitochondria in an early form of Lewy body (pale body) from Parkinson's disease patients. The results directly confirm that 26S dysfunction in neurons is involved in the pathology of neurodegenerative disease. The model demonstrates that 26S proteasomes are necessary for normal neuronal homeostasis and that 20S proteasome activity is insufficient for neuronal survival. Finally, we are providing the first reproducible genetic platform for identifying new therapeutic targets to slow or prevent neurodegeneration.
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| 2. |
- Ghomi, Erfan Rezvani, et al.
(författare)
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A collection of the novel coronavirus (COVID-19) detection assays, issues, and challenges
- 2021
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 7:6
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Forskningsöversikt (refereegranskat)abstract
- The global pandemic of COVID-19 has rapidly increased the number of infected cases as well as asymptomatic individuals in many, if not all the societies around the world. This issue increases the demand for accurate and rapid detection of SARS-CoV-2. While accurate and rapid detection is critical for diagnosing SARS-CoV-2, the appropriate course of treatment must be chosen to help patients and prevent its further spread. Testing platform accuracy with high sensitivity and specificity for SARS-CoV-2 is equally important for clinical, regional, and global arenas to mitigate secondary transmission rounds. The objective of this article is to compare the current detection technology and introduce the most accurate and rapid ones that are suitable for pandemic circumstances. Hence, the importance of rapid detection in societies is discussed initially. Following this, the current technology for rapid detection of SARS-CoV-2 is explained and classified into three different categories: nucleic acid-based, protein-based, and point of care (PoC) detection testing. Then, the current issues for diagnostic procedures in laboratories are discussed. Finally, the role of new technologies in countering COVID-19 is also introduced to assist researchers in the development of accurate and timely detection of coronaviruses. As coronavirus continues to affect human lives in a detrimental manner, the development of rapid and accurate virus detection methods could promote COVID-19 diagnosis accessible to both individuals and the mass population at patient care. In this regard, rRT-PCR and multiplex RT-PCR detection techniques hold promise.
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