Related Experiment Video
Updated: Jun 1, 2026
12:57
Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Protein aggregate spreading in neurodegenerative diseases: problems and perspectives
Seung-Jae Lee1, Hee-Sun Lim, Eliezer Masliah
1Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea. sjlee@konkuk.ac.kr
Neuroscience Research
|June 1, 2011
Summary
Protein aggregates spread between cells in neurodegenerative diseases like Alzheimer's and Parkinson's. Understanding this pathological spreading may lead to new diagnostic tools and therapies for these conditions.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Neurodegenerative diseases are characterized by the accumulation of specific protein aggregates.
- These aggregates, including tau, alpha-synuclein, and amyloid-beta, are increasingly recognized to spread between cells and brain regions.
- This cell-to-cell propagation was previously thought to be unique to prion disorders like Creutzfeldt-Jakob disease (CJD).
Purpose of the Study:
- To review recent advancements in understanding protein aggregate propagation in experimental models.
- To discuss the implications of pathological spreading in neurodegenerative diseases.
- To explore future perspectives and potential therapeutic strategies.
Main Methods:
- Review of recent experimental model systems studying protein aggregate propagation.
- Analysis of findings related to cell-to-cell spreading of aggregation-prone proteins.
- Discussion of implications for neurodegenerative disease progression and cell replacement therapies.
Main Results:
- Evidence suggests that aggregation-prone proteins can spread between cells and across brain regions, similar to prions.
- This propagation mechanism is implicated in the progressive deterioration observed in various neurodegenerative diseases.
- Aggregate spreading has been observed from host to grafted cells in Parkinson's disease cell transplantation studies.
Conclusions:
- Cell-to-cell propagation of protein aggregates may be a common mechanism underlying neurodegenerative diseases.
- Understanding these spreading mechanisms offers potential for developing novel diagnostic and therapeutic interventions.
- Further research into pathological spreading is crucial for advancing treatments for protein misfolding diseases.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:23Alzheimer Disease ll: Pathophysiology
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
01:24Parkinson Disease ll: Pathophysiology
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
01:15Parkinson's Disease: Overview
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is to...
01:29Alzheimer Disease l: Introduction
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...