Disease Information

General Information of the Disease (ID: DIS00256)

• Name: Parkinson disease
• ICD: ICD-11: 8A00

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Levedopa

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Leucine rich repeat kinase 2 (LRRK2) [1]

• Resistant Disease: Parkinson disease [ICD-11: 8A00.0]
• Molecule Alteration: Missense mutation; p.I2020T
• Resistant Drug: Levedopa
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Drug Resistance: Molecular docking analysis; Molecular dynamic simulation assay
• Mechanism Description: The deleterious mutations G2019S and I2020T in the kinase domain were playing a key role in causing resistance to drug levedopa.

Key Molecule: Leucine rich repeat kinase 2 (LRRK2) [1]

• Resistant Disease: Parkinson disease [ICD-11: 8A00.0]
• Molecule Alteration: Missense mutation; p.G2019S
• Resistant Drug: Levedopa
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Drug Resistance: Molecular docking analysis; Molecular dynamic simulation assay
• Mechanism Description: The deleterious mutations G2019S and I2020T in the kinase domain were playing a key role in causing resistance to drug levedopa.

Rotenone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Small nucleolar RNA host gene 14 (SNHG14) [2]

• Resistant Disease: Parkinson disease [ICD-11: 8A00.0]
• Molecule Alteration: Up-regulation; Interaction
• Resistant Drug: Rotenone
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: SNHG14/miR-133b/alpha -syn signaling pathway; Inhibition; hsa04933
• In Vitro Model: MN9D cells; N.A.; Mus musculus (Mouse); CVCL_M067
• In Vivo Model: C57BL/6 mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: Knockdown assay
• Experiment for Drug Resistance: Motor function assessment assay; CCK8 assay; ROS staining and detection assay
• Mechanism Description: Silence of SNHG14 mitigates dopaminergic neuron injury by down-regulating alpha-syn via targeting miR-133b, which contributes to improving PD.

Investigative Drug(s) 1 drug(s) in total

Cyperquat

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Non-coding RNA activated by DNA damage (NORAD) [3]

• Resistant Disease: Parkinson disease [ICD-11: 8A00.0]
• Molecule Alteration: Down-regulation; Expression
• Resistant Drug: Cyperquat
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SH-SY5Y cells; Abdomen; Homo sapiens (Human); CVCL_0019
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: XTT assay; TUNEL assay; caspase 3/7 activity fluorescence measurement; Total Reactive Oxygen Species assay; Pierce LDH Cytotoxicity assay
• Mechanism Description: NORAD downregulation was found to significantly deteriorate MPP+-induced cytotoxicity in SH-SY5Y cells.

Key Molecule: Nuclear paraspeckle assembly transcript 1 (NEAT1) [4]

• Resistant Disease: Parkinson disease [ICD-11: 8A00.0]
• Molecule Alteration: Up-regulation; Interaction
• Resistant Drug: Cyperquat
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SH-SY6Y cells; N.A.; .; N.A.
• Experiment for Molecule Alteration: Mimic assay; qRT-PCR; RNA pull down assay; RIP experiments assay; ELISA assay; Knockdown assay
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: NEAT1 may regulate MPP+ induced neuronal injury by targeting miR-124 in SH-SY5Y cells.

References

• Ref 1: Exploring the functional impact of mutational drift in LRRK2 gene and identification of specific inhibitors for the treatment of Parkinson disease .J Cell Biochem. 2018 Jun;119(6):4878-4889. doi: 10.1002/jcb.26703. Epub 2018 Mar 9. 10.1002/jcb.26703
• Ref 2: Dopaminergic neuron injury in Parkinson's disease is mitigated by interfering lncRNA SNHG14 expression to regulate the miR-133b/ Alpha-synuclein pathwayAging (Albany NY). 2019 Nov 4;11(21):9264-9279. doi: 10.18632/aging.102330. Epub 2019 Nov 4.
• Ref 3: Long noncoding RNA NORAD regulates MPP+-induced Parkinson's disease model cellsJ Chem Neuroanat. 2019 Nov;101:101668. doi: 10.1016/j.jchemneu.2019.101668. Epub 2019 Aug 14.
• Ref 4: NEAT1 regulates MPP(+)-induced neuronal injury by targeting miR-124 in neuroblastoma cellsNeurosci Lett. 2019 Aug 24;708:134340. doi: 10.1016/j.neulet.2019.134340. Epub 2019 Jun 19.