Alomone Labs is pleased to offer the Parkinson’s Disease Marker Antibody Kit (#AK-580). The Marker Kit contains Parkinson’s Disease marker antibodies, ideal for screening purposes.
|Product Name||Cat #||Size|
|ANT-027||1 x 50 µl|
|BLP-NT027||1 x 40 µg|
|ACC-201||1 x 50 µl|
|BLP-CC201||1 x 40 µg|
|ADR-001||1 x 50 µl|
|BLP-DR001||1 x 40 µg|
|ADR-001-GP (formerly AGP-100)||1 x 50 µl|
|BLP-DR001||1 x 40 µg|
|ADR-002||1 x 50 µl|
|BLP-DR002||1 x 40 µg|
|BLP-MT003||1 x 40 µg|
|ANT-014||1 x 50 µl|
|BLP-NT014||1 x 40 µg|
|APC-006||1 x 50 µl|
|BLP-PC006||1 x 0.12 mg|
|APC-006-GP (formerly AGP-013)||1 x 50 µl|
|BLP-PC006||1 x 0.12 mg|
|AGR-049||1 x 50 µl|
|BLP-GR049||1 x 40 µg|
|APZ-026||1 x 50 µl|
|BLP-PZ026||1 x 40 µg|
|ANR-102||1 x 50 µl|
|BLP-NR102||1 x 40 µg|
|ANT-028||1 x 50 µl|
|BLP-NT028||1 x 40 µg|
|APZ-035||1 x 50 µl|
|BLP-PZ035||1 x 40 µg|
|AMT-006||1 x 50 µl|
|BLP-MT006||1 x 40 µg|
Dopamine (DA) plays a major part in maintaining the stability of the basal ganglia network and is essential for the selection and processing of neuronal activity associated with normal movement. Alterations in dopaminergic signaling can have profound effects on cognitive and motor function, and are implicated in Parkinson’s Disease (PD). DA neurons act primarily at high affinity D2 receptors expressed by striatopallidal medium spiny neurons (MSNs), preventing them from responding too readily to uncoordinated cortical activity. When substantia nigra pars compacta SNc DA neurons transiently spike at high frequency in response to environmental cues, low affinity D1 receptors are activated, transiently enhancing the responsiveness of striatonigral MSNs to properly coordinated cortical ‘action commands’. In parallel, this burst of DA cell activity suppresses tonic activity in cholinergic interneurons, and potentially synergizes with postsynaptic D2 receptors on striatopallidal MSNs to prevent cortical glutamatergic signals shared with striatonigral MSNs from generating a state-transition, spiking and inappropriate action suppression. In this way, DA might gate the responsiveness of striatal output pathways to shared cortical glutamatergic action commands, preventing co-activation of incompatible action programs1.
GIRK channels are members of a large family of inwardly rectifying K+ channels. The weaver mouse has been used to investigate the role of GIRK channels in ataxia and Parkinson's disease. In these mice, GIRK2 (Kir3.2) channels contain a mutation that eliminates K+ selectivity and leads to degeneration of dopaminergic neurons in the midbrain substantia nigra pars compacta (SNc) and cerebellar granular neurons. The gain-of-function phenotype in dopaminergic neurons is of clinical interest owing to its similarity to the degeneration in Parkinson's disease. In dorsal root ganglion (DRG) cells, activation of the nerve growth factor receptor (also known as p75NTR) increases levels of phosphatidylinositol-4,5-bisphosphate, which activates GIRK2 channels and promotes programmed cell death through K+ efflux-induced apoptosis2.
DAT is a Na+/Cl--dependent transporter on presynaptic membranes of dopaminergic projections. DAT plays a critical role in regulating extracellular DA concentration and is considered a marker of DA terminal integrity. Degeneration of dopaminergic projections from the substantia nigra to the striatum results in loss of DAT. DAT concentration closely relates to striatal DA levels supporting its use as an imaging biomarker for PD thus making DAT-SPECT a sensitive modality to detect nigrostriatal degeneration3.
VMAT2 is an H+-ATPase antiporter that packages monoamines into small synaptic and dense core vesicles for their subsequent release from the neuron. Through this transmitter storage, VMAT2 also acts to sequester potentially harmful cytosolic DA storage. DA molecules left unpackaged are vulnerable to the creation of reactive oxygen species including hydroxyl radicals, superoxide, hydrogen peroxide, and dopamine-quinones that can result in function-altering cysteinyl adducts on cellular proteins. Post-mortem PD brains show dramatically reduced VMAT2-mediated vesicular filling. Additional findings, connecting VMAT2 and PD include higher cytosolic dopamine turnover in PD patients and a familial VMAT2 mutation that dramatically reduces vesicular filling and causes an infantile parkinsonian condition with profound motor and cognitive impairments. Moreover, there is mounting evidence that increased VMAT2 level or function protects against PD4.
Connexin 43 (Cx43) is an integral membrane protein. Each connexon or hemichannel is composed of six subunits called connexins. Docking of two apposed connexons from adjacent cells forms a gap junction (GJ). There is significant controversy regarding the exact role of Cx43 in PD. Rufer et al. found that total Cx43 mRNA and astroglial Cx43-immunoreactive GJ plaques are significantly increased in the striatum of MPTP-treated mice while in contrast, Kawasaki et al. showed that while Cx43 mRNA does not change, total and phosphorylated Cx43 protein levels increase in the striatum of rotenone-treated rats. In cultured astrocytes, rotenone induces the upregulation and trafficking of Cx43 protein to the membrane, which in turn leads to enhancement in GJ coupling5.
Homer1 is an important scaffold protein at postsynaptic density and has been demonstrated to play a central role in Ca2+ signaling in the central nervous system. Down-regulating Homer1 expression with specific small interfering RNA (siRNA) significantly suppresses LDH release, reduces Propidium iodide (PI) or Hoechst staining, increases the number of tyrosine hydroxylase (TH) positive cells and DA uptake, and attenuates apoptotic and necrotic cell death after MPP+ injury in in vitro models. Homer1 knockdown has been found to have protective effects against neuronal injury by reducing calcium overload mediated reactive oxygen species generation6.
α-synuclein is a soluble protein expressed primarily in neurons. The protein has an N-terminal helix, a central helix and an unorganized, negatively charged C-terminal. The N-terminal helix is characterized by high lipid affinity that anchors α-synuclein to membranes and assembles lipoprotein complexes, while the hydrophobic central region is prone to intermolecular interactions, which may promote the aggregation of soluble α-synuclein monomers into insoluble oligomers and polymers. Deletion or disruption of this region blocks this abnormal aggregation. Aggregated α-synuclein is the major component of Lewy bodies, the neuropathological hallmark of PD. Point mutations and multiplications in the SNCA gene cause autosomal dominant PD, supporting the pathogenetic role of α-synuclein in PD7.
LRRK2 is a large, multidomain protein, displaying both GTPase and kinase activities. Most PD-causing mutations related to LRRK2, notably R1441C/G and G2019S, cluster within these two enzymatic sites, which are surrounded by large protein–protein interacting domains. LRRK2 mutations are one of the most common genetic causes of PD: these mutations can account for as much as 40% of familial PD and its variants are also found within idiopathic cases. Unlike other PD-associated genes, LRRK2 Parkinsonism manifests similar clinical phenotypes to idiopathic PD, displaying strong age-dependent development of PD symptoms. Despite intense research effort over the past decade, the physiological function of LRRK2 and the contribution of mutations to PD remain largely elusive8.
GDNF (Glial-cell-derived neurotrophic factor) is a neurotrophic factor that has been extensively studied in experimental animal studies for its neuroprotective potential in PD. GDNF functions via a signaling complex constituted by RET tyrosine kinase, and the GDNF family receptor α (GFRα) 1. Initial in vitro studies show the capacity of GDNF to promote cell survival in mesencephalic cell cultures5.
- Surmeier, D.J. et al. (2007) Trends Neurosci. 30, 228.
- Luscher, C. and Slesinger, P.A. (2010) Nat. Rev. Neurosci. 11, 301.
- Ba, F. and Martin, W.R.W. (2015) Parkinsonism Relat. Disord. 21, 87.
- Lohr, K.M. and Miller, G.W. (2014) Expert Rev. Neurother. 14, 1115.
- Freitas-Andrade, M. and Naus, C.C. (2016) Neuroscience 323, 207.
- Chen, T. et al. (2013) Cell. Signal. 25, 2863.
- Malek, N. et al. (2014) Acta Neurol. Scand. 130, 59.
- Lee, H. et al. (2017) Biochem. Soc. Trans. 45, 131.
- Kirik, D. et al. (2017) Neurobiol. Dis. 97, 179.