Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Findings aid understanding of neurodegenerative diseases

30.09.2002


Northwestern University scientists have made a key molecular discovery that has implications for a wide range of diseases characterized by the loss of nerve function, including Huntington’s, Parkinson’s, Alzheimer’s and Lou Gehrig’s diseases, cystic fibrosis and Creutzfeldt-Jakob disease, the human form of mad cow disease.



The findings, which will be published in the Oct. 1 issue of Nature Cell Biology, could lead to an understanding of how to prevent these diseases and to the development of effective drugs.

All human neurodegenerative diseases have two things in common. First, misfolded and damaged proteins clump together to form toxic species that aggregate, destroy cell function and cause disease. Second, studies have shown that special protective proteins, called molecular chaperones, can suppress these toxic effects. This question remained: How do the chaperones and aggregates interact with each other?


A research team led by Richard I. Morimoto, John Evans Professor of Biology, now can answer that question. The researchers have become the first to view, in living cells and in real time, the interactions between the beneficial molecular chaperone Hsp70 and the damaging protein aggregate, shedding light on how the chaperone works to minimize aggregate growth.

"We now understand how the chaperone influences the aggregate’s toxic effect on the cell," said Morimoto. "We observed that the chaperone is binding to and then coming off the aggregate all the time. This dynamic relationship is unusual because the aggregate, the result of a genetic mutation, brings healthy and otherwise normal proteins to aggregate irreversibly with them. But this clearly is not the case with the molecular chaperone."

Instead, the molecular chaperone is allowed, for reasons not fully understood, to do its work preventing healthy proteins essential to cell function from being bound to the aggregate, a biochemical "black hole." The chaperone is continually sampling the aggregate to see what’s there and to release any healthy proteins from the aggregate’s clutches. This could suppress the aggregate’s growth, prolonging the life of the cell and delaying the onset of disease.

"These observations provide the first visual study of this cell survival activity," said Morimoto, whose team studied the chaperone Hsp70 (a heat shock protein) and polyglutamine aggregates, the type of protein aggregate responsible for Huntington’s disease. "The molecular chaperones are not like other proteins."

In order to visualize the behavior of chaperones and aggregates in an animal, the researchers use human tissue culture cells and C. elegans, a transparent roundworm whose biochemical environment is similar to that of human beings and whose genome, or complete genetic sequence, is known.

Although the Northwestern researchers are studying Huntington’s disease, these experimental models can be used to study other neurodegenerative diseases because of the common molecular components.

Proteins, made up of different combinations of amino acids, are basic components of all living cells. To do its job properly, each protein first must fold itself into the proper shape. In this delicate process, the protein receives its folding instructions from its amino acid sequence and is assisted by a class of proteins known as heat shock proteins or molecular chaperones that function to prevent misfolding, or, in the case of already misfolded proteins, to detect them and prevent their further accumulation.

In Huntington’s disease, for example, a mutated gene directs production of a protein with an increasing number of consecutive residues of the amino acid glutamine. When the number of residues expands past 40, the protein exhibits unusual biochemical properties, causing the protein to misfold. This results in a loss of function and protein aggregation -- in other words, disease.

"How do we use this new information about molecular chaperones to our advantage, to protect individuals from the molecular damage of disease?" said Morimoto. "That is our next challenge."

Related to this research, Morimoto reported in the August issue of Proceedings of the National Academy of Sciences that the appearance of aggregates and polyglutamine protein toxicity associated with Huntington’s disease in C. elegans can be suppressed by a genetic pathway that controls aging.

Megan Fellman | EurekAlert!
Further information:
http://www.nwu.edu/

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>