Related Experiment Videos
Kinase signalling in Huntington's disease.
Kathryn R Bowles1, Lesley Jones1
1MRC centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
Journal of Huntington'S Disease
|July 27, 2014
Summary
Huntington's disease (HD) involves altered kinase signaling, impacting cellular processes and leading to neurodegeneration. Understanding these complex pathway interactions is crucial for HD research and potential therapies.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Aberrant kinase signaling is implicated in Huntington's disease (HD) pathogenesis.
- Kinase pathways regulate critical cellular functions, and their imbalance contributes to HD phenotypes.
- Previous studies on kinase signaling in HD have yielded inconsistent results, potentially due to overlooking pathway integration and disease progression.
Purpose of the Study:
- To investigate the complex effects of mutant huntingtin (mHTT) on kinase signaling networks in Huntington's disease.
- To elucidate how dysregulated kinase activity contributes to HD pathology, including neurodegeneration.
Main Methods:
- Analysis of signal transduction pathways and kinase activity in HD models and human brain tissue.
- Collating and integrating existing data on mHTT's impact on kinase signaling networks.
Main Results:
- Huntington's disease (HD) is characterized by widespread alterations in signal transduction and kinase activity.
- Mutant huntingtin (mHTT) profoundly affects multiple pro- and anti-apoptotic kinases.
- This leads to dysregulation of complex interactions within cellular signaling networks.
Conclusions:
- Aberrant kinase signaling is a key mechanism underlying Huntington's disease (HD) pathology.
- The integration of multiple signaling pathways and their dynamic changes over time are critical for understanding HD.
- Further research into these complex kinase interactions may reveal therapeutic targets for HD.
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
11.5K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
11.5K
01:22Amplifying Signals via Enzymatic Cascade
16.7K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
16.7K
01:22PI3K/mTOR/AKT Signaling Pathway
5.1K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.1K
01:19Interactions Between Signaling Pathways
7.1K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.1K
02:33Hedgehog Signaling Pathway
9.6K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
9.6K
01:07MAPK Signaling Cascades
7.7K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.7K