A Strong Partnership with The Michael J. Fox Foundation for Parkinson’s Research

Reagents for PD

Pathogenesis of PD may be related to environmental and genetic factors, and exposure to toxins and gene mutations may underlie formation of brain lesions. Several mechanisms of PD pathology have been elucidated, including α-synuclein aggregation, oxidative stress, ferroptosis, mitochondrial dysfunction, neuroinflammation, and gut dysbiosis, while other key implicated proteins are being identified.

α-Synuclein is an abundant protein in brain neurons where it occurs in multiple forms. The unfolded form is thought to help maintain supply of synaptic vesicles and release of dopamine, a neurotransmitter critical for regulating voluntary and involuntary movements. However, aggregation and propagation of misfolded α-Synuclein protein to other neurons is believed to underlie PD pathology.

Mechanism of chaperone-controlled regulation of α-Synuclein function, conformation, and localization in mammalian cells¹.

Read below for our featured neuroscience reagents such as high-quality recombinant proteins for research into PD progression, immunoassays, and specific antibodies to detect native and aggregated forms of α-Synuclein.

Recombinant Proteins

Recombinant Human GAK (carrier-free)

Cyclin G-associated kinase (GAK), also known as auxilin 2, is a serine/threonine protein kinase that plays a crucial role in cellular processes, including membrane trafficking and cell cycle regulation. GAK regulates cyclin-dependent kinases and plays a key role in clathrin-mediated endocytosis via the interaction of the heat shock cognate protein 70. GAK is also involved in the regulation of protein degradation pathways, including the ubiquitin-proteasome system, and has emerged as a gene associated with Parkinson's disease.

The endo-lysosomal system is emerging as a key player in the pathogenesis of PD².

Recombinant Human INPP5F (carrier-free)

Inositol polyphosphate 5-phosphatase F (INPP5F), also known as phosphatidylinositide phosphatase SAC2, is a member of the INPP5 family. A key role of INPP5F is regulation of polyphosphoinositide metabolism and phosphoinositide signaling pathways by regulating the levels of inositol phospholipids. Positioned in the cytoplasm, INPP5F is closely associated with cellular membranes and participates in various cellular processes, including membrane trafficking, cytoskeleton dynamics, and signal transduction.

Mechanistically, INPP5F activates the Notch signaling pathway and upregulates c-MYC and cyclin E1 in hepatocellular carcinoma by interacting with ASPH. INPP5F also modulates the Akt/GSK-3β pathway by reducing Akt and GSK-3β phosphorylation levels. INPP5F is expressed in various tissues including heart, kidney, skeletal muscle, and brain. INPP5F contributes to tumorigenesis and tumor progression. INPP5F rs11789 6735 variant has been associated with an increased risk of Parkinson’s disease.

Stability testing for Recombinant Human INPP5F. One aliquot (Control) was stored at 4°C for 7 days, while another aliquot (4XF/T) was subjected to multiple freeze-thaw cycles by freezing at -80°C and thawing four times over a 7-day period. Each freeze-thaw cycle involved placing the sample on ice and slowly thawing it until no ice crystals remained in the tube. A minimum of 24 hours elapsed between each freeze and thaw event. Following treatment, the reduced samples (4 µg/lane) were separated by SDS-PAGE and stained with Coomassie brilliant blue dye. Lane M: Protein ladder (Cat. No. 773302).

Recombinant Human Cathepsin B (carrier-free)

Cathepsin B (CTSB) is a lysosomal cysteine protease. While most cathepsins are exclusively endopeptidases, CTSB exhibits both carboxypeptidase and endopeptidase activities. Cystatin C has been identified as an endogenous CTSB inhibitor. High CTSB protein levels and activities have been found in many tumors including breast, cervix, colon, stomach, glioma, lung, and thyroid tumors. CTSB can be secreted by tumor cells and is associated with the cell membrane of these cells. Membrane associated CTSB promotes extracellular matrix (ECM) degradation contributing to cancer motility and invasion. Many ECM proteins, including laminin, fibronectin, and collagen IV, are substrates of CTSB. CTSB can also activate pro-uPA/PLAU. Activated uPA promotes ECM digestion through serine protease plasminogen. Inhibition of CTSB can limit bone metastasis in breast cancer, making it an important anti-cancer drug target.

In animal models of PD, dysregulation of CTSB activity has been linked to neuronal cell death and the formation of Lewy bodies, a characteristic pathological feature of PD. CTSB has also been proposed as a new drug target for Alzheimer's disease because of its involvement in the production of β-amyloid (Aβ) peptides. Inhibition of CTSB was found to reduce brain Aβ peptides and improve memory in a mouse model with Alzheimer's disease.

CTSB also plays significant roles in immune responses including both T and B cell apoptosis, and Th1/Th2 polarization. CTSB is implicated in other pathological conditions including cardiovascular disease, multiple sclerosis, and arthritis.

Stability testing for Recombinant Human CTSB. One aliquot (Control) was stored at 4°C for 7 days, while another aliquot (4XF/T) was subjected to multiple freeze-thaw cycles by freezing at -80°C and thawing four times over a 7-day period. Each freeze-thaw cycle involved placing the sample on ice and slowly thawing it until no ice crystals remained in the tube. A minimum of 24 hours elapsed between each freeze and thaw event. Following treatment, the reduced samples (4 µg/lane) were separated by SDS-PAGE and stained with Coomassie brilliant blue dye. Lane M: Protein ladder (Cat. No. 773302).

Cathepsin secretion and intracellular and extracellular cathepsin function³. Autophagosomes are generated at subdomains of the endoplasmic reticulum, (ER) where cathepsins carry out different intracellular functions (A). Cathepsin function in the secretory autophagy pathway (B) is mediated by several proteins including Sec22b and Syntaxin 3 (STX3) and 4 (STX4) leading to secretion and downstream extracellular cathepsin function (C).

Recombinant Human GPNMB (carrier-free)

GPNMB, also known as osteoactivin, is a type I transmembrane glycoprotein involved in various cellular functions, including cell migration, proliferation, invasion, adhesion, and differentiation. GPNMB regulates differentiation and activities of both osteoblasts and osteoclasts in bone development and plays a key role in the pathogenesis of autoimmune disease, neurodegenerative diseases, and various malignancies.

GPNMB is a risk gene for Parkinson’s disease through its interaction with α-synuclein. In induced pluripotent stem cell-derived neurons, loss of GPNMB resulted in loss of ability to internalize α-Syn fibrils and develop α-Syn pathology. GPNMB has also been shown to be protective in neurons undergoing active degeneration.

GPNMB is also expressed in certain cancers including melanoma, glioma, and breast cancer cells. In addition, GPNMB expression has been detected in dendritic cells, melanocytes, and a variety of tissues within skin, heart muscle, lung, lymph node, breast, and colon. Notably, GPNMB expressed in macrophages negatively regulates inflammation.

Stability testing for Recombinant Human GPNMB. One aliquot (Control) was stored at 4°C for 7 days, while another aliquot (4XF/T) was subjected to multiple freeze-thaw cycles by freezing at -80°C and thawing four times over a 7-day period. Each freeze-thaw cycle involved placing the sample on ice and slowly thawing it until no ice crystals remained in the tube. A minimum of 24 hours elapsed between each freeze and thaw event. Following treatment, the reduced samples (4 µg/lane) were separated by SDS-PAGE and stained with Coomassie brilliant blue dye. Lane M: Protein ladder (Cat. No. 773302).

GPNMB intracellular signaling in physiological and inflammatory conditions⁴.

The release of a soluble GPNMB fragment, cleaved by the metalloproteinase ADAM10, releases a cascade of interactions with various molecular partners. These interactions include tyrosine kinase receptors, integrins, and heparan sulfate proteoglycans.

The role of GPNMB in inflammation is not clear due to it having both proinflammatory and anti-inflammatory roles. GPNMB's influence on adaptive immunity is mediated through its interaction with heparan sulfate proteoglycan syndecan-4. In the context of tumor biology, GPNMB binds to α5β1 fibronectin receptors, promoting tumor invasion and metastasis. GPNMB can be stimulated by various cytokines and growth factors, including granulocyte-macrophage-colony stimulating factors, Transforming growth factor- β, Interleukin-10, and interferon-γ.

Recombinant Human STK39 (carrier-free)

Serine/threonine kinase 39 (STK39) is a member of the Ste20-like kinase family and is thought to function in the cellular stress response pathway via activating p38 MAPK. STK39 is associated with Parkinson’s disease, hypertension, and autism, and plays a role in various cellular processes, including protein-protein interactions, cell signaling, and ion homeostasis.

STK39 levels have been linked to neuroprotection, particularly in Parkinson’s disease. Studies have demonstrated that STK39 rs6749447 is in linkage disequilibrium with the STK39 regulatory region variants rs1955337 and rs1474055, both of which are associated with Parkinson’s disease. STK39 expression have also been linked to tumor malignancy by playing crucial roles in migration, invasion, and proliferation of non-small cell type lung cancer cells.

Stability testing for Recombinant Human STK39. One aliquot (Control) was stored at 4°C for 7 days, while another aliquot (4XF/T) was subjected to multiple freeze-thaw cycles by freezing at -80°C and thawing four times over a 7-day period. Each freeze-thaw cycle involved placing the sample on ice and slowly thawing it until no ice crystals remained in the tube. A minimum of 24 hours elapsed between each freeze and thaw event. Following treatment, the reduced samples (4 μg/lane) were separated by SDS-PAGE and stained with Coomassie brilliant blue dye. Lane M: Protein ladder (Cat. No. 773302).

Immunoassays

Representative sandwich immunoassay standard curve generated using serial dilutions of LEGEND MAX Human α-Synuclein (Colorimetric) ELISA kit. Standard ranging from 10.2 pg/mL to 650 pg/mL.

Featured antibodies

Anti-Parkin (clone 5C3/Parkin), tested by western blotting on human and rat brain lysates (left). IHC staining of  purified anti-LRRK2 antibody (clone MC.028.83.76.242) on the formalin-fixed paraffin-embedded human pancreas tissue (middle). ICC staining of purified anti-Rab8 antibody (clone A18073A) on HeLa cells (right).