PdCure.org

  Providing resources and ideas for therapies and medical developments for Parkinson's disease:

 

Parkinson's Disease Research Lab Supplies, Resources, Software and Links:

The following are links to laboratory resources to help those researching Parkinson's disease.

Alpha-Synuclein Models:

Initiating Parkinson's alpha synuclein aggregation of pre-formed fibrils in animal models or just testing in-vitro, will require one of these products.

  • StressMarq Biosciences: Alpha Synuclein Pre-formed Fibrils and Monomers
    StressMarq manufactures active proteins and antibodies for PD research. This includes active alpha synuclein pre-formed fibrils (PFFs) that can induce endogenous alpha synuclein phosphorylation and Lewy body formation in neuronal cell culture or for in vitro oligomerization studies. These fibrils seed the formation of new fibrils from active alpha synuclein monomers. Stabilized oligomers are also available, and can induce toxicity in cell models. Also available: A53T mutation Alpha-Synuclein monomers and PFFs (A53T refers to an alpha-synuclein genetic variation in which the 53rd amino acid is changed from Alanine to Threonine). Support products for Alpha-Synuclein protocols.
    Distributors:
  • rPeptide: Alpha Synuclein Preformed Fibrils
    These preformed fibrils of α-synuclein may be used as a model for the pathogenic form of α-synuclein in numerous neuropathies. Sourced from E. coli, α-synuclein fibrils were prepared and confirmed by thioflavin assay and electron microscopy.
Laboratory equipment

Mouse Models:

Mice used in research are typically genetically modified to express a mutation being studied or to possess a portion of a human DNA sequence in order to react with a human response. After all, the purpose of genetic modification is to develop therapies for humans and not mice. Animals which possess the native and foreign DNA sequences are termed "transgenic".

National Institutes of Health Guide for the care and use of laboratory animals (pdf)
Laboratory mouse

Inducing Parkinson's Pathology in Mouse Models:

Once a mouse model has been chosen, Parkinson's can be induced with the neurotoxin MPTP or by the injection of human alpha-synuclein pre-formed fibrils (PFF) to seed aggregation of rat alpha-synuclein proteins. Once seeded, propagation of protein aggregates spread along axons.

Also see Testing movement disorders in mice

Laboratory mouse injection

Chemical, Molecular and Biological Databases:

  • PubChem - chemical information
    One can also download current chelator compound digital models (DMSA, DMPS, NBMI, ALA, MiaDMSA, Glutathione, etc)
  • BindingDB - molecules with drug-like properties and their binding affinities
  • UniProt - protein sequence and function. Used for AI "learning".
  • NIH: Chemical structures database (chemical and molecular models including nucleotides, carbohydrates, lipids, peptides, chemically-modified macromolecules, etc)
  • ChEMBL - database of bioactive molecules with drug-like properties. ChEMBL primarily stores compound-target interactions (how a small molecule binds to a protein or biological target) rather than direct patient drug-drug interactions.
  • NCATS - An open-science platform that shares real-time drug screening data, protocols, and chemical datasets for emerging public health needs and other diseases.
    The National Center for Advancing Translational Sciences (NCATS) provides several key public databases and data portals to support preclinical research, drug discovery, and clinical studies.
  • CartBlanche - an interface to ZINC-22, a free database of commercially-available compounds for virtual screening and ligand discovery.
  • RCSB: Protein Data Bank (PDB) - hosted by Rutgers, UC San Diego, UC San Diego Supercomputer Center, UC San Francisco
  • Human Protein Atlas
Also see SMILES - specification in the form of a line notation for describing the structure of chemical species using ASCII strings
  • VAE: A SMILES Variational Autoencoder - a deep learning model that translates discrete molecular structures written in SMILES format into a continuous numerical string for automated drug and material design.

Chemistry and Molecular Databases

Software Models and Resources:

Gone are the days of counting cells in an image. We have software to do that mundane work. Tinker toy chemical models have been replaced by 3D computer models. Even analytics are automated with purpose built data analysis tools.

  • Google AlphaFold - pairing DeepMind AI and protein folding
  • Fold.it - visual protein folding software for protein research and design
  • National Institute of Health (NIH) software: (free open source)
    • ImageJ - Image processing and analysis in Java - microglia item count and astrocytes densities
  • Zeiss: software:
    • Axiovision - image analysis
    • ZEN lite - image acquisition from microscope cameras, image processing and analysis
  • GraphPad:
    Prism - analysis and graphing solution purpose-built for scientific research
  • Certara:
    Phoenix WinNonlin - data processing, graphing and charting, report generation. Pharmacokinetic/pharmacodynamic (PK/PD), and toxicokinetic (TK) modeling.
  • CADD: Computer Aided Drug Design
  • SDF: Structure Data Format - text based chemical structure data file
    Software which can read SDF files:
    • Avogadro - free open source for MS/Win, Mac and Linux. Define, model and visualize 3D molecules. Interfaces with many computational chemistry tools
    • DataWarrior - free open source
    • OpenEye Scientific VIDA
    • iMol - free open source
    • Jmol - free open source Java based viewer for 3D chemical structures, vibration frequency mode animations, etc
    • IQmol - free open source. MS/Win, Mac, Linux. Generate models of molecules.
    • Molekel - free open source
    • ChemSpotlight - free open source
    • Open Babel - free open source
    • SDFReader - free open source
    Tools: Progenesis SDF Studio - A free tool to view, merge and repair SDF and MOL files.
  • Computational Chemistry Tools:
    • Gaussian - molecular mechanics, quantum chemistry, coupled cluster calculations
    • ORCA - quantum chemistry, coupled cluster calculations
    • LAMMPS - for solid-state materials (metals, semiconductors) and soft matter (biomolecules, polymers) and coarse-grained or mesoscopic systems.
    • GROMACS - open-source software suite for high-performance molecular dynamics and output analysis.
    • Swiss-Model - 3D protein modeling
      works with other tools:
      • Blast - compares protein sequences to sequence databases
      • HHBlits - iterative protein sequence searching
      • MolProbity - validation for 3D structures of proteins
      • HPEPDOCK - predict complex structure between a protein and a peptide
        [server]
      • HDOCK server - Protein-protein and protein-DNA/RNA docking
    • MOPAC: Molecular Orbital PACkage - semiempirical quantum chemistry - free open source for MS/Win, Mac and Linux
    • GAMESS: General Atomic and Molecular Electronic Structure System - quantum chemical calculations. Many code forks exist with huge differences. Free open source for MS/Win, Mac and Linux
    ORCA and Gaussian tend to be more accurate. MOPAC and GAMESS tend to be less computationally demanding.
  • VMD: Visual Molecular Dynamics - molecular visualization and animation. Free open source for MS/Win, Mac and Linux. Like Avogadro but more sophisticated
  • PyMol - molecular visualization and animation. Free open source for MS/Win, Mac and Linux. Maintained by Schrödinger.
  • De Novo Software; FCX Express - raw flow cytometry data (number of cells or particles in a liquide flow) to report charts
Alpha-synuclein protein 6PEO
Protein Database: Cryo-EM structure of alpha-synuclein H50Q Narrow Fibril

Statistical Software and Resources:

Statistical software from commercial sources and now more than ever, available as free open source software.

Gibbs statistical sampling
Gibbs statistical sampling

Measurment Equipment:

Data gethering equipment.

Lab measurement equipment

Lab Equipment and Chemicals:

General suppliers of biological research equipment.

  • Bio-Rad - digital biology, genomics, diagnostics, cell biology, lab equipment and supplies
  • Millipore SiGMa - lab supplies, EIA kits, substrates, ...
  • Vector Laboratories - reagents, immunofluorescence, staining, detection, etc
  • Phoenix Pharmaceuticals Inc - peptides, assay kits, EIA kits, etc. Exendin-4 (Heloderma suspectum) EIA Ki (measurement).
  • Qiagen - RNA isolation kits, DNA methylation analysis, RNA/DNA sequencing, etc
  • Abcam - Assay kits, reagents and antibodies.
    LDH Assay Kit - Cell death/Cytotoxicity - detection of LDH released from damaged cells used to assess the level of plasma membrane damage in a cell population
  • Tocris - reagents
  • Takara - reagents for cloning, DNA ligation kits
Lab equipment - Creative Commons

Stains:

Positive staining and fluorescent tagging are used to visualize and identify the entity of interest (cell type, organelles, etc). Stains can have chemical affinity, a chemical reaction, immunization marker, bind to a protein, etc Negative staining has the opposite effect, to highlight everything but the entity of interest, thus making the entity of interest identifiable. Staining can also be categorized as "simple" or "differential" where simple staining uses one type of stain at a time while differential staining uses multiple stains where different entity types appear in different colors. The method of staining will also be influenced by the type of microscopy used (optical, electron) as well as the frequency and wavelength of light.

Also see: Staining Products:
Cells stained - Creative Commons

Stem cells:

Stem cells - Creative Commons

Antibodies:

Antibodies - Creative Commons

Links:


Lab Terms and Acronyms:

Term or AcronymDescription
ELISAEnzyme Linked Immunosorbent Assay: analytical measurement method that uses antibodies to detect the presence of peptides, proteins, antigens or hormones
EIAEnzyme Immunoassay: used to detect antigens or antibodies by producing an enzyme triggered color change. Often used interchangably with the acronym ELISA
assayAn assay is a lab procedure to measure the presece or amount of an entity (drug, biochemical substance, cell, ...)
antigenAn antigen is a molecule, present on the outside of a pathogen, that can be bound by an antigen-specific antibody. Antigens typically trigger an immune response
antibodyAn antibody is a Y shaped protein used to identify and neutralize pathogens (bacteria and viruses). The antibody recognizes the antigen which identifies the pathogen
substrateThe chemical being observed in a chemical reaction
reagentThe substance added to a system to cause a chemical reaction
De Novo DesignThe process of creating completely new molecules, proteins, or drugs from scratch using physical rules and computers, rather than copying existing natural templates.
ESCembryonic stem cells
PBSphosphate buffered saline
QED scoreQuantitative Estimate of Drug-likeness. Numerical value from 0 to 1 that measures how likely a molecule is to become an oral drug. A score of 1 means the molecule has ideal properties, while 0 means the properties are completely unfavorable. Takes into account Molecular weight, Lipophilicity, polar surface areas, number of rotatable bonds, number of aromatic rings, etc... (Bickerton et al, 2012)
TgTransgenic: lab animals with some of their DNA substituted with human DNA to better model drug efficacy for human consumption
immunofluorescenceis an assay which is used primarily on biological samples and used to detect antigens using specific antibodies
immunoblotting(western blotting) is an assay using antigen-antibody interaction for the detection and characterization of specific proteins