KEGG   PATHWAY: map05022
Entry
map05022                    Pathway                                
Name
Pathways of neurodegeneration - multiple diseases
Description
Neurodegeneration is generally defined as progressive, irreversible loss of neurons, which may affect either the peripheral or central nervous system (CNS). Neurodegenerative diseases (NDs) include highly debilitating illnesses, such as Alzheimer (AD), Parkinson disease (PD), amyotrophic lateral sclerosis, Huntington disease, spinocerebellar ataxias, and prion diseases (PrD). The hallmark event, which is thought to be at the root of these diseases, is the progressive accumulation of misfolded protein aggregates. Major basic processes include abnormal protein dynamics due to deficiency of the ubiquitin-proteosome-autophagy system, oxidative stress and free radical formation, endoplasmic reticulum stress, mitochondrial dysfunction and (secondary) disruptions of axonal transport.
Class
Human Diseases; Neurodegenerative disease
Pathway map
map05022  Pathways of neurodegeneration - multiple diseases
map05022

Reference
  Authors
Gan L, Cookson MR, Petrucelli L, La Spada AR
  Title
Converging pathways in neurodegeneration, from genetics to mechanisms.
  Journal
Nat Neurosci 21:1300-1309 (2018)
DOI:10.1038/s41593-018-0237-7
Reference
  Authors
Dugger BN, Dickson DW
  Title
Pathology of Neurodegenerative Diseases.
  Journal
Cold Spring Harb Perspect Biol 9:a028035 (2017)
DOI:10.1101/cshperspect.a028035
Reference
  Authors
Jellinger KA
  Title
Basic mechanisms of neurodegeneration: a critical update.
  Journal
J Cell Mol Med 14:457-87 (2010)
DOI:10.1111/j.1582-4934.2010.01010.x
Reference
  Authors
Jellinger KA
  Title
Recent advances in our understanding of neurodegeneration.
  Journal
J Neural Transm (Vienna) 116:1111-62 (2009)
DOI:10.1007/s00702-009-0240-y
Reference
  Authors
Van Bulck M, Sierra-Magro A, Alarcon-Gil J, Perez-Castillo A, Morales-Garcia JA
  Title
Novel Approaches for the Treatment of Alzheimer's and Parkinson's Disease.
  Journal
Int J Mol Sci 20:E719 (2019)
DOI:10.3390/ijms20030719
Reference
  Authors
Ross CA, Poirier MA
  Title
Protein aggregation and neurodegenerative disease.
  Journal
Nat Med 10 Suppl:S10-7 (2004)
DOI:10.1038/nm1066
Reference
  Authors
Soto C, Pritzkow S
  Title
Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases.
  Journal
Nat Neurosci 21:1332-1340 (2018)
DOI:10.1038/s41593-018-0235-9
Reference
  Authors
Dantuma NP, Bott LC
  Title
The ubiquitin-proteasome system in neurodegenerative diseases: precipitating factor, yet part of the solution.
  Journal
Front Mol Neurosci 7:70 (2014)
DOI:10.3389/fnmol.2014.00070
Reference
  Authors
Zheng C, Geetha T, Babu JR
  Title
Failure of ubiquitin proteasome system: risk for neurodegenerative diseases.
  Journal
Neurodegener Dis 14:161-75 (2014)
DOI:10.1159/000367694
Reference
  Authors
Park H, Kang JH, Lee S
  Title
Autophagy in Neurodegenerative Diseases: A Hunter for Aggregates.
  Journal
Int J Mol Sci 21:E3369 (2020)
DOI:10.3390/ijms21093369
Reference
  Authors
Malik BR, Maddison DC, Smith GA, Peters OM
  Title
Autophagic and endo-lysosomal dysfunction in neurodegenerative disease.
  Journal
Mol Brain 12:100 (2019)
DOI:10.1186/s13041-019-0504-x
Reference
  Authors
Metaxakis A, Ploumi C, Tavernarakis N
  Title
Autophagy in Age-Associated Neurodegeneration.
  Journal
Cells 7:E37 (2018)
DOI:10.3390/cells7050037
Reference
  Authors
Vidal RL, Matus S, Bargsted L, Hetz C
  Title
Targeting autophagy in neurodegenerative diseases.
  Journal
Trends Pharmacol Sci 35:583-91 (2014)
DOI:10.1016/j.tips.2014.09.002
Reference
  Authors
Menzies FM, Fleming A, Caricasole A, Bento CF, Andrews SP, Ashkenazi A, Fullgrabe J, Jackson A, Jimenez Sanchez M, Karabiyik C, Licitra F, Lopez Ramirez A, Pavel M, Puri C, Renna M, Ricketts T, Schlotawa L, Vicinanza M, Won H, Zhu Y, Skidmore J, Rubinsztein DC
  Title
Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities.
  Journal
Neuron 93:1015-1034 (2017)
DOI:10.1016/j.neuron.2017.01.022
Reference
  Authors
Chu CT
  Title
Mechanisms of selective autophagy and mitophagy: Implications for neurodegenerative diseases.
  Journal
Neurobiol Dis 122:23-34 (2019)
DOI:10.1016/j.nbd.2018.07.015
Reference
  Authors
Kim I, Xu W, Reed JC
  Title
Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities.
  Journal
Nat Rev Drug Discov 7:1013-30 (2008)
DOI:10.1038/nrd2755
Reference
  Authors
Doyle KM, Kennedy D, Gorman AM, Gupta S, Healy SJ, Samali A
  Title
Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders.
  Journal
J Cell Mol Med 15:2025-39 (2011)
DOI:10.1111/j.1582-4934.2011.01374.x
Reference
  Authors
Halliday M, Hughes D, Mallucci GR
  Title
Fine-tuning PERK signaling for neuroprotection.
  Journal
J Neurochem 142:812-826 (2017)
DOI:10.1111/jnc.14112
Reference
  Authors
Rozpedek-Kaminska W, Siwecka N, Wawrzynkiewicz A, Wojtczak R, Pytel D, Diehl JA, Majsterek I
  Title
The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases.
  Journal
Int J Mol Sci 21:E2108 (2020)
DOI:10.3390/ijms21062108
Reference
  Authors
Hetz C, Mollereau B
  Title
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases.
  Journal
Nat Rev Neurosci 15:233-49 (2014)
DOI:10.1038/nrn3689
Reference
  Authors
Bezprozvanny I
  Title
Calcium signaling and neurodegenerative diseases.
  Journal
Trends Mol Med 15:89-100 (2009)
DOI:10.1016/j.molmed.2009.01.001
Reference
  Authors
Ureshino RP, Erustes AG, Bassani TB, Wachilewski P, Guarache GC, Nascimento AC, Costa AJ, Smaili SS, Pereira GJDS
  Title
The Interplay between Ca(2+) Signaling Pathways and Neurodegeneration.
  Journal
Int J Mol Sci 20:E6004 (2019)
DOI:10.3390/ijms20236004
Reference
  Authors
Golpich M, Amini E, Mohamed Z, Azman Ali R, Mohamed Ibrahim N, Ahmadiani A
  Title
Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment.
  Journal
CNS Neurosci Ther 23:5-22 (2017)
DOI:10.1111/cns.12655
Reference
  Authors
Morfini GA, Burns M, Binder LI, Kanaan NM, LaPointe N, Bosco DA, Brown RH Jr, Brown H, Tiwari A, Hayward L, Edgar J, Nave KA, Garberrn J, Atagi Y, Song Y, Pigino G, Brady ST
  Title
Axonal transport defects in neurodegenerative diseases.
  Journal
J Neurosci 29:12776-86 (2009)
DOI:10.1523/JNEUROSCI.3463-09.2009
Reference
  Authors
Gibbs KL, Greensmith L, Schiavo G
  Title
Regulation of Axonal Transport by Protein Kinases.
  Journal
Trends Biochem Sci 40:597-610 (2015)
DOI:10.1016/j.tibs.2015.08.003
Reference
  Authors
Millecamps S, Julien JP
  Title
Axonal transport deficits and neurodegenerative diseases.
  Journal
Nat Rev Neurosci 14:161-76 (2013)
DOI:10.1038/nrn3380
Reference
  Authors
Sleigh JN, Rossor AM, Fellows AD, Tosolini AP, Schiavo G
  Title
Axonal transport and neurological disease.
  Journal
Nat Rev Neurol 15:691-703 (2019)
DOI:10.1038/s41582-019-0257-2
Reference
  Authors
Perlson E, Maday S, Fu MM, Moughamian AJ, Holzbaur EL
  Title
Retrograde axonal transport: pathways to cell death?
  Journal
Trends Neurosci 33:335-44 (2010)
DOI:10.1016/j.tins.2010.03.006
Related
pathway
map00190  Oxidative phosphorylation
map03050  Proteasome
map04020  Calcium signaling pathway
map04120  Ubiquitin mediated proteolysis
map04137  Mitophagy - animal
map04140  Autophagy - animal
map04141  Protein processing in endoplasmic reticulum
map04142  Lysosome
map04210  Apoptosis
map04310  Wnt signaling pathway
map04724  Glutamatergic synapse
map04933  AGE-RAGE signaling pathway in diabetic complications
KO pathway
ko05022   

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