China
Africa
Explore chapters and articles related to this topic
Mitochondria in Huntington’s Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Finally, since because huntingtin facilitates and mutant huntingtin likely inhibits dynein/dynactin-mediated vesicular transport, it is plausible to speculate drugs targeting a reduction in the size of huntingtin aggregates may restore the functionality of huntingtin.
Manipulating the Intracellular Trafficking of Nucleic Acids
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Kathleen E. B Meyer, Lisa S. Uyechi, Francis C. Szoka
The motor proteins are believed to attach to receptor proteins anchored in organelle membranes, and two such receptor proteins have been identified and are currently under investigation (73). The kinectin protein is thought to join kinesin to the organelle membrane. Kinectin is predicted by its amino acid sequence to form a coiled-coil motif and is anchored in the membrane by its N-terminal sequence (74). Antibodies to kinectin, blocking potential binding sites for kinesin, inhibit plus-end-directed organelle movement in vitro by 90% (75). The dynactin complex, consisting of 10 different polypeptides, is capable of interacting with cytoplasmin dynein as well as microtubules, kinetochores, and membranes (73), yet the molecular events involved in attachment have not been elucidated. The interaction of microtubules with membranous organelles also appears to involve linker protein, or CLIPS, that bind to membranes via protein receptors (73,76). It remains to be determined whether additional kinectin- or dynactinlike proteins exist, which receptor proteins are found on specific organelles, and how organelle movement is orchestrated.
Instability of Human Mitochondrial DNA, Nuclear Genes and Diseases
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
The ability to move is particularly important in neurons as they are the longest cells in the organism. Axonal mitochondrial transport goes along microtubules. From cell body to synapses (anterograde transport) it is conducted via kinesins and is mediated by MFN2 retrograde transport (from synapses to cell body) mitochondria move by dynein and dynactin. Both processes require energy.
Targeted sequencing approach: Comprehensive analysis of DNA methylation and gene expression across blood and brain regions in suicide victims
Published in The World Journal of Biological Psychiatry, 2023
Katarina Kouter, Tomaž Zupanc, Alja Videtič Paska
RNA from hippocampus was isolated using the phenol–chloroform extraction method using TRIzol reagent (Thermo Scientific, USA). Concentration and integrity were measured using NanoDrop ND1000 (Thermo Scientific, USA), Agilent RNA chip and 2100 BioAnalyzer (Agilent, USA). RIN values of pooled samples for suicide victims and control group were 6.9 and 6.1, respectively. RNA was transcribed into cDNA using Maxima First Strand cDNA Synthesis Kit (Thermo Scientific, USA) as per manufacturer recommendations. For qPCR TaqMan Fast Advanced master mix and exon spanning TaqMan Gene Expression Assays (both Applied Biosystems, USA) were used. Detailed information in the Supplementary Table S5. Reference genes used were beclin 1 (BECN1) and dynactin subunit 2 (DCTN2), selected based on our previous validation (publication in preparation, data available on request). Assays were validated before use. All reactions were carried out in triplicates, using ViiA 7 Real-Time PCR System (Applied Biosystems, USA). Each well contained 18.75 ng of cDNA. qPCR was performed following MIQE guidelines (Bustin et al. 2009).
The contribution of C. elegans neurogenetics to understanding neurodegenerative diseases
Published in Journal of Neurogenetics, 2020
Joseph J. H. Liang, Issa A. McKinnon, Catharine H. Rankin
Altered vesicular transport is also implicated in ALS pathologies. Slowed cargo transport is suggested to be an early pre-symptomatic phenotype observed in a mouse model of ALS (Williamson & Cleveland, 1999), and mutations in the human and mouse dynein-dynactin complex replicate phenotypes seen in ALS (Puls et al., 2003). In addition, a Drosophila study reported the downregulation of dynactin-1 and impairment in the fusion of autophagosomes in a TDP-43-depleted model (Xia et al., 2016). Indeed, in characterizing the motor neuron-specific gene expression profiles of sALS patients, dynactin-1(DCTN1) was downregulated in motor neurons from an early disease stage (Jiang et al., 2005; Jiang et al., 2007). DCTN1 is a vital component of dynactin, a multi-member complex associated with dynein in its role as a molecular motor for retrograde transport. An early study on the worm ortholog of DCTN1, dnc-1, and other components in the complex had interesting parallels with other ALS disease models (Koushika et al., 2004). Of note, an increase in size and number of protein aggregates in neuronal processes, reduced locomotion and a reduced lifespan were observed in C. elegans dynein complex mutants (Koushika et al., 2004). Ikenaka et al. (2013) further investigated the role of dnc-1 with motor neuron-specific RNAi and observed an increased number of autophagosomes, a remarkable pathological feature of ALS patients. The group had since utilized this model as a behavior-based drug screening system to identify drugs that can ameliorate dnc-1 mutant phenotypes (Ikenaka et al., 2019).
Syntaphilin mediates axonal growth and synaptic changes through regulation of mitochondrial transport: a potential pharmacological target for neurodegenerative diseases
Published in Journal of Drug Targeting, 2023
Qing-Yun Wu, Hui-Lin Liu, Hai-Yan Wang, Kai-Bin Hu, Ping Liao, Sen Li, Zai-Yun Long, Xiu-Min Lu, Yong-Tang Wang
Cytoplasmic Dynein regulates the retrograde transport of mitochondria along microtubules from the axon terminal to the soma. Dynein is composed of multiple peptide chains and usually needs to combine with Dynactin to form a complex to bind mitochondria for axonal transport [26]. Mutations of Dynein reduce the distance and duration of retrograde mitochondrial transport in Drosophila flight motoneurons. It is interesting to note that disruption of the Dynactin complex does not interfere with motor binding to the outer mitochondrial membrane, but does block bidirectional mitochondrial transport, suggesting that Dynactin plays an important role in regulating bidirectional transport driven by KIF5 and Dynein [28].