Are tangles as toxic as they look?
Tara L Spires-Jones1, Katherine J Kopeikina, Robert M Koffie
1Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA. tspires@partners.org
Journal of Molecular Neuroscience : MN
|June 4, 2011
Summary
Neurofibrillary tangles, hallmarks of Alzheimer's disease, may not be toxic to neurons. Recent studies, including in-vivo imaging, challenge the long-held view that these tau protein aggregates directly harm brain cells.
Area of Science:
- Neuroscience
- Cell Biology
- Neuropathology
Background:
- Neurofibrillary tangles, composed of hyperphosphorylated tau protein, are a hallmark of Alzheimer's disease and tauopathies.
- Previous studies suggested tangles were toxic, correlating their accumulation with neuronal and synapse loss, and dementia.
- Emerging research questions the direct toxicity of aggregated tau species, including tangles.
Purpose of the Study:
- To review recent experimental evidence on the toxicity of aggregated versus soluble tau protein.
- To re-evaluate the role of neurofibrillary tangles in neuronal dysfunction and death in tauopathies.
- To present findings from in-vivo imaging studies of tangle formation and the fate of tangle-bearing neurons.
Main Methods:
- Review of recent experimental studies on tau protein toxicity.
- In-vivo imaging of neurofibrillary tangles in the intact brain through a cranial window in mouse models.
- Longitudinal observation of tangle formation and the survival of neurons containing tangles.
Main Results:
- Recent advances challenge the traditional view of neurofibrillary tangles as directly toxic species.
- In-vivo imaging allows direct observation of tangle dynamics and their impact on neurons.
- The fate of neurons bearing tangles is being directly investigated, providing new insights into tauopathy progression.
Conclusions:
- The direct toxicity of neurofibrillary tangles to neurons is increasingly being questioned.
- In-vivo imaging provides a powerful tool to study tau pathology in real-time.
- Further research is needed to fully understand the role of tangles and soluble tau in neurodegeneration.
Related Concept Videos
01:36Types of Toxins
Humans continually engage with an environment rich in potentially harmful chemicals. These are introduced to our bodies through inhalation, ingestion, or skin contact. These chemicals exist in various forms, such as air and environmental pollutants, agricultural chemicals, organic solvents, and heavy metals.
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
01:26Toxic Reactions: Overview
When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
01:26Physical Properties of Amines
Amines with low molecular weight are usually gaseous at room temperature, while those with high molecular weight are liquid or solids in nature. Usually, low molecular weight amines have a rotten fish-like smell. Diamines typically have a pungent smell. For instance, cadaverine and putrescine, depicted in Figure 1, are two molecules responsible for decaying tissue.
01:29Tetanus
Tetanus is a life-threatening neurological disorder characterized by persistent muscle contractions and spastic paralysis. It is caused by Clostridium tetani, a motile, Gram-positive, rod-shaped, obligate anaerobe. These bacteria produce terminal endospores, giving them a distinctive “lollipop” or “tennis-racket” appearance. They thrive in anaerobic environments, such as those found in deep puncture wounds.Once introduced into the body, the spores germinate into vegetative cells. These cells...
01:23Toxicity Testing in Animals
Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...
01:24Drug Toxicity: Dose-Dependent Reactions
Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...