Nano
Sun Mar 15, 2020 1:2
Gold Nanoparticles Uncover Amyloid Fibrils
TEHRAN (FNA)- One of the characteristics of Alzheimer's disease is the presence of knot-like structures between brain cells. These are called "amyloid fibrils" and are formed by the notorious amyloid beta peptide and Tau protein, which are two of the most sought-after targets for the development of therapies to treat Alzheimer's and similar diseases.

Both amyloid beta and Tau are normally produced in the brain. However, these proteins can begin to get tangled up with each other to form bulky fibril structures. When this happens, they give rise to disorders like Alzheimer's disease and other neurodegenerative diseases.

The fibril structures spread throughout the brain by moving from one cell to another. This is thought to lead to degeneration of neurons, causing brain damage and cognitive impairments like memory loss, and research efforts have generally focused on blocking these processes to slow the progression of the disease.

We now know that these amyloid fibrils can exist in multiple shapes and structures that exhibit different distinct properties which may explain why Alzheimer's and Parkinson's disease patients show different clinical symptoms. Therefore, capturing this diversity and correlating with disease symptoms in humans or the biological activity of these species in disease models has important implications for understanding disease mechanisms and developing novel therapies and diagnostics.

Given the importance of amyloid fibrils, there have been many efforts to visualize them in as much detail as possible in order to gain insights about their structure. Unraveling their structural details could possibly lead to detection of weak spots that could be targeted for treatment and pave the way for developing more reliable diagnostic tools. Despite much work, however, imaging and capturing the diversity of fibrils in biological samples has proven to be very difficult due to their complex nature and heterogeneity.

The way of gold (nanoparticles)

Now, scientists from the groups of Francesco Stellacci and Hilal Lashuel at EPFL have found a solution. In a breakthrough paper published in PNAS, the researchers show that gold amphiphilic anionic nanoparticles with a diameter around 3 nm, have a unique ability to efficiently label the edge of amyloid fibrils in a hydrated state. This makes the visualization of the diverse amyloid fibrils easier.

The research project was led by PhD student Urszula Cendrowska and Dr Paulo J. Silva.

This was possible by imaging the nanoparticles-decorated fibrils using a specialized form of TEM called "cryogenic transmission electron microscopy" (cryo-EM). The main difference here is that in cryo-EM the sample -- here the fibrils -- is first rapidly frozen to a very low temperature and can be visualized in its "natural" state without having to be fixed or stained beforehand.

Between the highly efficient binding of gold nanoparticles and the capabilities of cryo-EM, the scientists were able to obtain images of fibrils and unmask their diversity with unprecedented clarity. This included fibrils grown in the lab as well as from actual postmortem tissues of patients.

"Our findings reveal a striking morphological difference between the fibrils produced in cell-free systems and those isolated from patients," says Stellacci. "This supports the current view that the physiologic environment plays a major role in determining different types of amyloid fibrils."

"These advances pave the way for elucidating the structural basis of amyloid strains and toxicity," says Lashuel. "The nanoparticles are powerful and desperately needed tools for rapid imaging and profiling of amyloid morphological polymorphism in different types of samples under cryo-conditions, especially complex samples isolated from human-derived pathological aggregates."

 

 

 

Bottom top
‘Washington Has No Idea About Who It Deals with': Erdogan Brushes Off US Criticism over S-400

TEHRAN (FNA)- Turkish President Recep Tayyip Erdogan confirmed that Ankara does not intend to abandon the S-400 missile systems purchased from Russia.
‘Rigged Election?’ Trump Seizes on Biden's Latest Gaffe, Boasting About 'Most Extensive, Inclusive VOTER FRAUD' Organization

TEHRAN (FNA)- Democratic presidential candidate Joe Biden's remark that his party has created “the most extensive voter fraud organization” has reinforced the former VP’s “gaffe-machine” status, giving the Republicans a free gotcha moment.
Iran Reports 6,191 New COVID-19 Cases

TEHRAN (FNA)- The Iranian health ministry announced on Sunday that 6,191 new cases of coronavirus infection have been reported across the country during the past 24 hours, adding that 296 patients have passed away in the same period of time.
GC Spokesman: Iran Not Interested in US Presidential Election

TEHRAN (FNA)- Spokesman of Iran’s Guardian Council Abbasali Kadkhodayee underlined that the Islamic Republic is not interested in interfering in the US presidential election, and blasted the media hype by the West in this regard.
Pakistan PM: French President Encouraged Islamophobia

TEHRAN (FNA)- The Pakistani prime minster added his voice to the growing criticism of the French president for "encouraging Islamophobia" following the killing of a teacher who showed cartoons of the Prophet Mohammad (PBUH) to his pupils.
Biden Gains as Suburban Women, Elderly Voters Look to Dump Trump

TEHRAN (FNA)- Joe Biden’s hopes of reaching the White House could rest on two crucial demographic groups that appear to be deserting President Donald Trump: elderly people and suburban women.
Iranian Army Conducts Military Drills along Northwestern Borders

TEHRAN (FNA)- The Iranian Army Ground Force units staged a one-day drill along the country's Northwestern border regions on Sunday.
Iran Calls for Broadening of Bilateral Ties with Bolivia

TEHRAN (FNA)- Iranian President Hassan Rouhani called for the expansion of mutual cooperation with Bolivia in different fields.
Officials: Top al-Qaeda Leader Killed in Eastern Afghanistan

TEHRAN (FNA)- A senior al-Qaeda commander has been killed by Afghan security forces in the central city of Ghazni, security officials said.
COVID-19: Italy Reports Highest Single-Day Spike

TEHRAN (FNA)- Italy reported 19,644 new coronavirus cases on Saturday, the highest single-day spike since the start of the pandemic.
IRGC Commander Warns against Geopolitical Border Change in Regions Around Iran

TEHRAN (FNA)- Islamic Revolution Ground Force Commander Brigadier General Mohammad Pakpour said any threat that harms people’s security and calm will receive Iran’s countermeasure, but further warned that his country would not tolerate any change in the geopolitical borders in regions close to Iran.
Palestinian Groups Condemn Macron’s Defense of Anti-Islam Cartoons

TEHRAN (FNA)- Palestinian resistance groups based in the Israeli-besieged Gaza Strip have blasted French President Emmanuel Macron for defending offensive cartoons of Islam’s Prophet Mohammad (PBUH).
Iran Condemns Terrorist Attack in Afghanistan

TEHRAN (FNA)- Iranian Foreign Ministry Spokesman Saeed Khatibzadeh condemned a terrorist attack in Afghanistan, saying that the Afghan students have fallen victim to the ugly violence and unending war they had never chosen.
Iran: Arbitrary Detention of Palestinians by Israel Should Stop

TEHRAN (FNA)- The Iranian Foreign Ministry condemned the Zionist regime’s unjust imprisonment of hundreds of Palestinians, urging the immediate release of hunger striker Maher Al-Akhras.
350kg of Opium Seized in Central Iran in 4 Operations

TEHRAN (FNA)- Police forces of the Central Province of Yazd confiscated 350 kg of illegal drugs in four separate operations, according to the local police commander Brigadier General Abbas Ali Behdani Fard.