Equivalencies: 0 | Classes: 0 | Children: 3 | Explore

Entity

Name
Neurodegenerative Diseases
Namespace
mesh
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/mesh-names.belns

Appears in Networks 16

In-Edges 24

p(HGNC:CHRNA7) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

AChRs have been linked to many neurodegenerative disorders [13,47–60]. PubMed:22040696

path(MESH:"Protein Aggregation, Pathological") association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Protein aggregation is recognized as a hallmark of neurodegenerative disease by the consistent appearance of detergent-insoluble inclusions and aggregates in the nucleus and cytoplasm of neurons. PubMed:25784053

p(HGNC:LRRK2, var("p.Gly2019Ser")) increases path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Finally, Parkinson’s disease patients carrying familial mutations in the parkin gene, and some of those with the LRRK2 G2019S mutation, show neuronal degeneration in the absence of Lewy body formation [28, 50]. PubMed:28803412

Annotations
Confidence
Medium

p(HGNC:PRKN, var("?")) increases path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Finally, Parkinson’s disease patients carrying familial mutations in the parkin gene, and some of those with the LRRK2 G2019S mutation, show neuronal degeneration in the absence of Lewy body formation [28, 50]. PubMed:28803412

Annotations
Confidence
Medium

p(HGNCGENEFAMILY:Calpains) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Calpains are calcium-activated cytosolic cysteine proteases. Two isoforms differentiated and named by their sensitivities to calcium (i.e., μ-calpain and m-calpain, also called calpain-1 and calpain-2) are abundant in the central nervous system, and respond to micromolar and millimolar concentrations of calcium, respectively (45). Calpain has been implicated in a number of neurodegenerative diseases [for a review, see (46)]. PubMed:24027553

p(HGNC:STUB1) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Several E3 Ub ligases, such as CHIP, Parkin, RNF182, may have roles in AD and other neurodegenerative diseases (Shimura et al., 2004; Khandelwal et al., 2011; Lei et al., 2012). PubMed:23528736

p(HGNC:ATXN3, var("?")) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Another DUB known to be mutated in familial neurodegenerative diseases is Ataxin-3 in the polyglutamine (polyQ) spinocerebellar ataxia type 3 (Kawaguchi et al., 1994). PubMed:23528736

p(HGNC:PRKN) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Several E3 Ub ligases, such as CHIP, Parkin, RNF182, may have roles in AD and other neurodegenerative diseases (Shimura et al., 2004; Khandelwal et al., 2011; Lei et al., 2012). PubMed:23528736

p(HGNC:RNF182) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Several E3 Ub ligases, such as CHIP, Parkin, RNF182, may have roles in AD and other neurodegenerative diseases (Shimura et al., 2004; Khandelwal et al., 2011; Lei et al., 2012). PubMed:23528736

p(HGNC:UCHL1, var("?")) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Mutations in ubiquitin C-terminal hydrolase L1 (UCH-L1) have been proposed to have a role in various neurodegenerative diseases including AD, although the causality of mutations in this gene in Parkinson’s disease is now considered doubtful (Healy et al., 2006; Hutter et al., 2008). PubMed:23528736

bp(MESH:Aging) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Aging is the biggest risk factor for developing a neurodegenerative disease, but the specific factors which cause these predominantly sporadic diseases are still under investigation (Reeve et al., 2014). PubMed:29311797

path(MESH:"Immune System Diseases") increases path(MESH:"Neurodegenerative Diseases") View Subject | View Object

At the same time, we have learnt that immune dysregulation contributes to prevalent diseases in Western societies such as atherosclerosis, type 2 diabetes, cancer and neurodegenerative diseases. PubMed:23702978

Annotations
Confidence
High

a(HBP:"protein aggregates") positiveCorrelation path(MESH:"Neurodegenerative Diseases") View Subject | View Object

The presence of aberrant protein aggregates is common to neurodegenerative diseases PubMed:29758300

bp(GO:"neuron death") association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

With neurons profoundly relying on macroautophagy for clearance of toxic protein aggregates, impairment in the proteolytic systems ultimately results in progressive neuronal death, a common feature in several neurodegenerative diseases [27]. PubMed:29758300

bp(GO:"regulation of endosome size") association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Neuronal endosome enlargement, which is not characteristically observed in other major neurodegenerative diseases, develops in pyramidal neurons of the neocortex at a stage when plaques and tangles are restricted only to the hippocampus (Braak stage 2) and not in brains of similarly aged individuals free of AD-like hippocampal pathology (Cataldo et al. 1997, 2000). PubMed:22908190

bp(GO:autophagy) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

It has also been suggested that autophagy plays a role in the initiation or progression of some neurodegenerative diseases [20]. PubMed:18930136

bp(GO:autophagy) negativeCorrelation path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Insight into the role of autophagy in neurodegeneration has been provided by studies indicating that: 1) some neurodegenerative disease-related proteins are degraded by autophagy, 2) impairment of autophagy promotes neurodegeneration in animal models and several human neurodegenerative diseases, and 3) manipulation of autophagy modifies phenotypes in animal models of neurodegeneration. PubMed:18930136

p(MESH:Proteins, pmod(HBP:misfolding)) positiveCorrelation path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Many neurodegenerative diseases are characterized by accumulation of misfolded protein deposits in affected brain regions, suggesting a failure in the cell’s degradative capacity [19]. PubMed:18930136

bp(GO:"aggresome assembly") association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Indeed, aggresome formation represents one such process employed by a cell to discard misfolded proteins (125) and has been implicated in neurodegenerative diseases (126). PubMed:29191965

bp(GO:autophagy) decreases path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Therefore, a common pathogenesis underlying all these NDDs disorders has been linked to autophagy inhibition due to mTOR hyperactivation PubMed:30061532

act(p(HGNC:MTOR)) positiveCorrelation path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Therefore, a common pathogenesis underlying all these NDDs disorders has been linked to autophagy inhibition due to mTOR hyperactivation PubMed:30061532

Out-Edges 19

path(MESH:"Neurodegenerative Diseases") association p(HGNC:CHRNA7) View Subject | View Object

AChRs have been linked to many neurodegenerative disorders [13,47–60]. PubMed:22040696

path(MESH:"Neurodegenerative Diseases") association path(MESH:"Protein Aggregation, Pathological") View Subject | View Object

Protein aggregation is recognized as a hallmark of neurodegenerative disease by the consistent appearance of detergent-insoluble inclusions and aggregates in the nucleus and cytoplasm of neurons. PubMed:25784053

path(MESH:"Neurodegenerative Diseases") increases path(MESH:"Proteostasis Deficiencies") View Subject | View Object

Loss of neuronal proteostasis, a common feature of the aging brain, is accelerated in neurodegenerative disorders, including different types of tauopathies PubMed:29024336

path(MESH:"Neurodegenerative Diseases") increases path(MESH:"Proteostasis Deficiencies") View Subject | View Object

It is well accepted that loss of proteostasis occurs gradually with age and underlies the basis of severe neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and other types of frontotemporal dementia (Prahlad & Morimoto, 2009; Voisine et al., 2010; Morimoto & Cuervo, 2014) PubMed:29024336

path(MESH:"Neurodegenerative Diseases") association p(HGNCGENEFAMILY:Calpains) View Subject | View Object

Calpains are calcium-activated cytosolic cysteine proteases. Two isoforms differentiated and named by their sensitivities to calcium (i.e., μ-calpain and m-calpain, also called calpain-1 and calpain-2) are abundant in the central nervous system, and respond to micromolar and millimolar concentrations of calcium, respectively (45). Calpain has been implicated in a number of neurodegenerative diseases [for a review, see (46)]. PubMed:24027553

path(MESH:"Neurodegenerative Diseases") association p(HGNC:STUB1) View Subject | View Object

Several E3 Ub ligases, such as CHIP, Parkin, RNF182, may have roles in AD and other neurodegenerative diseases (Shimura et al., 2004; Khandelwal et al., 2011; Lei et al., 2012). PubMed:23528736

path(MESH:"Neurodegenerative Diseases") association p(HGNC:PRKN) View Subject | View Object

Several E3 Ub ligases, such as CHIP, Parkin, RNF182, may have roles in AD and other neurodegenerative diseases (Shimura et al., 2004; Khandelwal et al., 2011; Lei et al., 2012). PubMed:23528736

path(MESH:"Neurodegenerative Diseases") association p(HGNC:RNF182) View Subject | View Object

Several E3 Ub ligases, such as CHIP, Parkin, RNF182, may have roles in AD and other neurodegenerative diseases (Shimura et al., 2004; Khandelwal et al., 2011; Lei et al., 2012). PubMed:23528736

path(MESH:"Neurodegenerative Diseases") association p(HGNC:UCHL1, var("?")) View Subject | View Object

Mutations in ubiquitin C-terminal hydrolase L1 (UCH-L1) have been proposed to have a role in various neurodegenerative diseases including AD, although the causality of mutations in this gene in Parkinson’s disease is now considered doubtful (Healy et al., 2006; Hutter et al., 2008). PubMed:23528736

path(MESH:"Neurodegenerative Diseases") association p(HGNC:ATXN3, var("?")) View Subject | View Object

Another DUB known to be mutated in familial neurodegenerative diseases is Ataxin-3 in the polyglutamine (polyQ) spinocerebellar ataxia type 3 (Kawaguchi et al., 1994). PubMed:23528736

path(MESH:"Neurodegenerative Diseases") association bp(MESH:Aging) View Subject | View Object

Aging is the biggest risk factor for developing a neurodegenerative disease, but the specific factors which cause these predominantly sporadic diseases are still under investigation (Reeve et al., 2014). PubMed:29311797

path(MESH:"Neurodegenerative Diseases") positiveCorrelation a(HBP:"protein aggregates") View Subject | View Object

The presence of aberrant protein aggregates is common to neurodegenerative diseases PubMed:29758300

path(MESH:"Neurodegenerative Diseases") association bp(GO:"neuron death") View Subject | View Object

With neurons profoundly relying on macroautophagy for clearance of toxic protein aggregates, impairment in the proteolytic systems ultimately results in progressive neuronal death, a common feature in several neurodegenerative diseases [27]. PubMed:29758300

path(MESH:"Neurodegenerative Diseases") association bp(GO:"regulation of endosome size") View Subject | View Object

Neuronal endosome enlargement, which is not characteristically observed in other major neurodegenerative diseases, develops in pyramidal neurons of the neocortex at a stage when plaques and tangles are restricted only to the hippocampus (Braak stage 2) and not in brains of similarly aged individuals free of AD-like hippocampal pathology (Cataldo et al. 1997, 2000). PubMed:22908190

path(MESH:"Neurodegenerative Diseases") positiveCorrelation p(MESH:Proteins, pmod(HBP:misfolding)) View Subject | View Object

Many neurodegenerative diseases are characterized by accumulation of misfolded protein deposits in affected brain regions, suggesting a failure in the cell’s degradative capacity [19]. PubMed:18930136

path(MESH:"Neurodegenerative Diseases") association bp(GO:autophagy) View Subject | View Object

It has also been suggested that autophagy plays a role in the initiation or progression of some neurodegenerative diseases [20]. PubMed:18930136

path(MESH:"Neurodegenerative Diseases") negativeCorrelation bp(GO:autophagy) View Subject | View Object

Insight into the role of autophagy in neurodegeneration has been provided by studies indicating that: 1) some neurodegenerative disease-related proteins are degraded by autophagy, 2) impairment of autophagy promotes neurodegeneration in animal models and several human neurodegenerative diseases, and 3) manipulation of autophagy modifies phenotypes in animal models of neurodegeneration. PubMed:18930136

path(MESH:"Neurodegenerative Diseases") association bp(GO:"aggresome assembly") View Subject | View Object

Indeed, aggresome formation represents one such process employed by a cell to discard misfolded proteins (125) and has been implicated in neurodegenerative diseases (126). PubMed:29191965

path(MESH:"Neurodegenerative Diseases") positiveCorrelation act(p(HGNC:MTOR)) View Subject | View Object

Therefore, a common pathogenesis underlying all these NDDs disorders has been linked to autophagy inhibition due to mTOR hyperactivation PubMed:30061532

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.