Pathogenesis of Parkinson's Disease

A technique used to determine the amount or concentration of a specific molecule or protein in a sample.

Specialized cells in the brain responsible for supporting and protecting neurons.

A type of protein transporter found in the brain that helps remove glutamate, a neurotransmitter, from the synapse.

A method used to separate proteins based on their size and charge.

A molecule involved in cellular communication, especially in the brain, often associated with learning and memory.

A type of protein involved in the formation of amyloid plaques, which are associated with Alzheimer's disease.

A technique used to isolate specific proteins from a complex mixture, usually using antibodies.

A method used to visualize and analyze proteins within a sample.

A process used to isolate and purify astrocytes from a mixed cell population. It involves the selective removal of other cell types, such as microglia.

A protein specifically expressed in astrocytes, used as a marker to identify them.

A method of staining tissue sections with antibodies that target specific proteins, enabling visualization of cells and structures in the tissue.

A solution used to preserve and protect biological samples, often for microscopy. It prevents degradation and keeps the tissue intact.

Red blood cell-derived extracellular vesicles (RBC-EVs) isolated from patients with Parkinson's disease (PD) contain elevated levels of oligomeric α-synuclein (α-syn).

RBC-EVs isolated from PD patients were injected twice a week into A53T mice, a model for Parkinson's disease.

After a six-week injection regimen, researchers found that A53T mice injected with PD RBC-EVs showed increased levels of oligomeric α-syn in their brains compared to A53T mice receiving RBC-EVs from healthy controls.

These results suggest that RBC-EVs from PD patients can promote the spread of α-syn aggregation in the brains of mice.

Oligomeric α-synuclein refers to smaller groups of α-syn molecules that can form clumps.

Extracellular vesicles (EVs) are small sacs released by cells that can carry cargo, such as proteins, to other cells.

A53T mice are genetically engineered mice that are a model for studying Parkinson's disease.

The presence of misfolded proteins in body fluids, even before symptoms appear, suggests a potential role in disease development.

Red blood cell-derived extracellular vesicles (RBC-EVs) are small vesicles that bud off from red blood cells and carry cargo, including misfolded proteins.

Oligomeric α-synuclein, a misfolded protein found in RBC-EVs, is linked to the development and progression of Parkinson's disease.

Studies have indicated that misfolded α-synuclein can be detected in the blood and even red blood cells of healthy individuals, suggesting potential early signs of disease.

Red blood cell-derived extracellular vesicles (RBC-EVs) can potentially disrupt the protective function of astrocytes, which are star-shaped cells in the brain that play a crucial role in maintaining brain health.

The presence of misfolded α-synuclein in RBC-EVs is linked to neuronal damage, suggesting a possible role in the spread of pathology in Parkinson's disease.

Recent research suggests that misfolded α-synuclein can spread from the periphery (outside the brain) to the brain, highlighting the importance of studying peripheral factors in neurodegenerative diseases.

The study of RBC-EVs and their role in carrying misfolded proteins provides valuable insights into the early stages of Parkinson's disease and potential avenues for future research and treatment.

A technique that utilizes proximity ligation (PL) to detect and quantify specific protein interactions within cells.

This assay is widely used to understand the behavior of α-syn and its interactions.

Cells are fixed with formaldehyde to preserve cellular structures and proteins, then treated with blocking solution to prevent non-specific antibody binding.

The assay utilizes primary antibodies that specifically target the intracellular domain of EAAT2 and α-syn.

Secondary antibodies are tagged with oligonucleotides, which combine to form a circular DNA molecule when the two antibodies bind in close proximity.

This assay measures the uptake of H-d-aspartate, a neurotransmitter, by cultured astrocytes.

Dynasore is a drug that inhibits the function of dynamin, a protein involved in vesicle trafficking, which plays a role in the uptake of neurotransmitters.

This assay involves separating proteins based on their molecular weight, using electrophoresis followed by transferring them onto a membrane for antibody binding.

α-synuclein (α-syn) is a protein found in abundance in the brain, primarily in neurons. It is involved in the regulation of synaptic transmission, and its aggregation is known to be associated with Parkinson's disease. When α-synuclein forms oligomers, it can lead to neurotoxicity.

Red blood cell-derived extracellular vesicles (RBC-EVs) are tiny packets of biomolecules released from red blood cells. They contain various proteins, lipids, and nucleic acids and play a role in communication between cells. In the context of Parkinson's disease, RBC-EVs carrying α-synuclein have been implicated in the spread of the disease.

Astrocytes are star-shaped glial cells in the brain. They play a crucial role in maintaining the brain's environment, including providing structural support, regulating blood flow, and influencing neuronal activity. In Parkinson's disease, astrocytes may contribute to the progression of the disease by accumulating α-synuclein.

Oligomeric α-synuclein refers to the aggregation of α-synuclein into small clusters. These clusters are thought to be particularly toxic to neurons and contribute significantly to the pathogenesis of Parkinson's disease. Oligomers can form in various brain regions and affect different cell types, including astrocytes.

The blood-brain barrier (BBB) is a highly selective membrane that protects the brain from harmful substances circulating in the blood. However, in Parkinson's disease, the BBB can become compromised, allowing molecules like α-synuclein to enter the brain and contribute to the disease.

GFAP (glial fibrillary acidic protein) is a marker protein that is found in abundance in astrocytes. GFAP expression is commonly used to identify and visualize astrocytes in brain tissue. Researchers often use GFAP staining to examine the distribution and potential dysfunction of astrocytes in various neurological conditions, including Parkinson's disease.

In Parkinson's disease, α-synuclein, primarily in its oligomeric form, can be found accumulating within the processes of astrocytes, specifically in areas like the cortex, striatum, and cerebellum. These regions are crucial for motor control and cognitive functions, and the accumulation of α-synuclein within astrocytes in these regions potentially contributes to the disease's progression.

Astrocytes, which are star-shaped glial cells with processes extending throughout brain tissue, play a crucial role in maintaining the brain environment. They act as a support system for neurons and help regulate the brain's microenvironment. By accumulating α-synuclein in their processes, astrocytes may be involved in the spread and progression of Parkinson's disease.