Neurodegeneration
Alzheimer's Disease | Parkinson's Disease| Huntington's Disease | Amyotrophic Lateral Sclerosis
Neurodegenerative diseases refer to a group of age-associated conditions with progressive loss of neuronal structure and function, often accompanied by aberrant protein accumulation, resulting in cognitive disability, motor deficits and dementia. The four most common neurodegenerative diseases - Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis (ALS) - each have different clinical presentations and affect different neuronal populations and brain areas. However, commonalities have been identified between the diseases, suggesting that abnormal protein aggregation and failure of autophagy, mitochondrial dysfunction and oxidative stress, as well as inflammatory environment and reactive microglia contribute to the development of all these diseases. Learn about Exosomes in Neurodegenerative Disease and their potential as a source of biomarkers for early detection of these diseases.
Most Common Neurodegenerative Diseases and Their Pathologies
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Alzheimer's Disease
Alzheimer’s disease (AD) is marked by a progressive cognitive impairment including memory loss and behavioral changes. Numerous environmental and generic risk factors have been associated with developing this generally sporadic disease. AD is characterized by amyloid-beta accumulation in extracellular neural tissues, as well as intracellular neurofibrillary tangles consisting of phosphorylated tau protein. The result is a deterioration of cholinergic neurons and loss of synaptic function in the hippocampus and cerebral cortex.
Major Protein Targets Involved in AD
| Gene | Protein Target | Role in Disease |
|---|---|---|
| APP |
Integral membrane protein that is sequentially processed by beta-secretase and gamma-secretase to produce amyloid-beta that can form oligomers and lead to amyloid plaques formation. |
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| PSEN1/PSEN2 | Presenilin-1 Presenilin-2 |
Facilitate gamma-secretase cleavage of APP. Mutations in presenilins increase production of the aggregation prone amyloid-beta variant (Aβ42). |
| APOE/APOE4 |
Major cholesterol carrier, supports lipid transport. ApoE isoforms differentially regulate amyloid-beta aggregation and clearance in the brain. APOE ε4 allele is associated with increased risk of developing AD. |
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| MAPT | Tau |
A neuronal microtubule associated protein found in axons. Promotes tubulin polymerization and stabilizes microtubules. Hyperphosphorylated tau is a major component of neurofibrillary tangles. |
beta Amyloid Antibody (MOAB-2) [NBP2-13075] - IHC analysis of a formalin fixed paraffin embedded tissue section of human brain (Alzheimer's disease, hippocampus) using 1:200 dilution of anti-beta Amyloid antibody (clone MOAB-2). The staining was developed with HRP labeled anti-mouse secondary antibody and DAB reagent, and nuclei of cells were counter-stained with Hematoxylin (Catalog # 5222). This beta Amyloid antibody specifically stained the cells with Abeta 42/ Abeta aggregates.
Presenilin-1 was detected in immersion fixed paraffin-embedded sections of human brain (medulla) using Mouse Anti-Human Presenilin-1 N-Terminal Fragment Monoclonal Antibody (Catalog # MAB149) at 1.7 µg/mL for 1 hour at room temperature followed by incubation with the Anti-Mouse IgG VisUCyte™ HRP Polymer Antibody (Catalog # VC001). Tissue was stained using DAB (brown) and counterstained with Hematoxylin (Catalog # 5222). Specific staining was localized to neuronal cell bodies.
Tau was detected in immersion fixed paraffin-embedded sections of human Alzheimer's brain using Mouse Anti-Tau Monoclonal Antibody (Catalog # MAB3494) at 15 µg/mL overnight at 4 °C. Before incubation with the primary antibody, tissue was subjected to heat-induced epitope retrieval using Antigen Retrieval Reagent-Basic (Catalog # CTS013). Tissue was stained using the Anti-Mouse HRP-DAB Cell & Tissue Staining Kit (brown; Catalog # CTS002) and counterstained with Hematoxylin (Catalog # 5222). Specific staining was localized to neuronal cell bodies and processes.
Parkinson's DiseaseParkinson’s disease (PD) is a common neurodegenerative disease characterized by the loss of midbrain dopaminergic neurons, mainly in the substantia nigra. It is defined by the presence of alpha-synuclein aggregates (Lewy bodies) and accumulation of defective mitochondria, leading to neuronal death. PD patients display a variety of motor symptoms such as resting tremors, rigidity and postural instability, along with non-motor symptoms including depression, sleep disorder and olfactory dysfunction. Sporadic forms of the disease constitute more than 90% of cases and the onset occurs over the age of 60. Currently, there is no cure for PD, but its motor symptoms can be alleviated temporarily with dopamine inducing approaches. New therapies concentrate on neuroprotective and disease-modifying strategies. Major Protein Targets Involved in PD
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PINK1 Antibody [NBP1-49678] - Stain in paraffin embedded mouse brain.
Tyrosine Hydroxylase was detected in immersion fixed mouse embryonic stem cells differentiated into dopaminergic neurons using Mouse Anti-Human/Mouse Tyrosine Hydroxylase Monoclonal Antibody (Catalog # MAB7566) at 10 µg/mL for 3 hours at room temperature. Cells were stained using the NorthernLights™ 557-conjugated Anti-Mouse IgG Secondary Antibody (red; Catalog # NL007). Cells were double stained using the NorthernLights™ 637-conjugated Mouse Anti-Neuron-specific beta-III Tubulin Monoclonal Antibody (white; Catalog # NL1195V). Cells were counterstained with DAPI (blue). Specific staining of Tyrosine Hydroxylase was localized to cytoplasm of dopaminergic neurons.
Huntington's DiseaseHuntington’s disease (HD) is marked by a progressive degeneration of neurons of the striatum and cortex. The disease is familial and follows an autosomal dominant inheritance pattern. It is characterized by a polyglutamine repeat expansion in the huntingtin protein that results in formation of neuronal inclusions and subsequent neuronal loss. This leads to movement, psychiatric and cognitive impairments. Patients are usually diagnosed at 40 years of age and have life expectancy of around 15 years. Currently, no cure exists for the disease. Major Protein Targets Involved in HD
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HAP1 Antibody (1B6) [NB110-74569] - Staining of rat hypothalamus.
BDNF was detected in immersion fixed paraffin-embedded sections of human spinal cord using Chicken Anti-Human BDNF Antigen Affinity-purified Polyclonal Antibody (Catalog # AF248) at 15 µg/mL overnight at 4 °C. Tissue was stained using HRP-DAB detection (brown) and counterstained with hematoxylin (blue).
Amyotrophic Lateral SclerosisAmyotrophic Lateral Sclerosis (ALS; commonly know as Lou Gehrig's disease) is a disease of degeneration of motor neurons in the brain and the spinal cord. It is the third most common neurodegenerative disease and the most common motor neuron disease. Symptoms include loss of control of muscle movement as well as muscle weakness, atrophy, twitching and cramps. The onset of the disease occurs at approximately 60 years old and patients survive on average three years from diagnosis. Most cases of ALS are sporadic and involve a number of genes, with further genes still likely to be discovered. However, 60% of familial ALS can be attributed to mutations in four genes: SOD1, TDP-43/TARDBP, FUS and C9orf72. Aberrant autophagy and RNA metabolism are two processes heavily implicated in disease progression. Protein aggregates are also a common feature of ALS. Major Protein Targets Involved in ALS
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TDP-43/TARDBP Antibody [NB110-55376] - Total protein from HeLa, MCF7 and mouse brain was separated on a 12% gel by SDS-PAGE, transferred to PVDF membrane and blocked in 5% non-fat milk in TBST. The membrane was probed with 1.0 μg/mL anti-TARDBP in 1% block buffer and detected with an anti-rabbit HRP secondary antibody using chemiluminescence.
C9orf72 Antibody [NBP2-47146] - IHC analysis of a formalin fixed paraffin embedded tissue section of mouse brain using C9orf72 antibody (NBP2-47146) at 1:300 dilution with HRP-DAB detection and Hematoxylin (blue; Catalog # 5222)counterstaining. The antibody generated strong/specific cytoplasmic signal in the neurons and other cell types in the tested section.
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Content developed by Michalina Hanzel, PhD Postdoctoral Associate at The Rockefeller University.