Reprogramming the Brain’s Cleaning Crew to Mop Up Alzheimer’s Disease

The discovery of how to shift damaged brain cells from a diseased state into a healthy one presents a potential new path to treating Alzheimer’s and other forms of dementia, according to a new study from researchers at UC San Francisco (UCSF). The research focuses on microglia, cells that stabilize the brain by clearing out damaged neurons and the protein plaques often associated with dementia and other brain diseases. These cells are understudied, despite the fact that changes in them are known to play a significant role Alzheimer’s and other brain diseases, said Martin Kampmann, PhD, senior author on the study, which appears in Nature Neuroscience.

Microglia (green) derived from human stem cells

Now, using a new CRISPR method we developed, we can uncover how to actually control these microglia, to get them to stop doing toxic things and go back to carrying out their vitally important cleaning jobs,”  Kampmann said. “This capability presents the opportunity for an entirely new type of therapeutic approach.

Most of the genes known to increase the risk for Alzheimer’s disease act through microglial cells. Thus, these cells have a significant impact on how such neurodegenerative diseases play out, said Kampmann. Microglia act as the brain’s immune system. Ordinary immune cells can’t cross the blood-brain barrier, so it’s the task of healthy microglia to clear out waste and toxins, keeping neurons functioning at their best. When microglia start losing their way, the result can be brain inflammation and damage to neurons and the networks they form. Under some conditions, for example, microglia will start removing synapses between neurons. While this is a normal part of brain development in a person’s childhood and adolescent years, it can have disastrous effects in the adult brain.

Over the past five years or so, many studies have observed and profiled these varying microglial states but haven’t been able to characterize the genetics behind them. Kampmann and his team wanted to identify exactly which genes are involved in specific states of microglial activity, and how each of those states are regulated. With that knowledge, they could then flip genes on and off, setting wayward cells back on the right track. Accomplishing that task required surmounting fundamental obstacles that have prevented researchers from controlling gene expression in these cells. For example, microglia are very resistant to the most common CRISPR technique, which involves getting the desired genetic material into the cell by using a virus to deliver it. To overcome this, Kampmann’s team coaxed stem cells donated by human volunteers to become microglia and confirmed that these cells function like their ordinary human counterparts. The team then developed a new platform that combines a form of CRISPR, which enables researchers to turn individual genes on and off – and which Kampmann had a significant hand in developing – with readouts of data that indicate functions and states of individual microglia cells.

Through this analysis, Kampmann and his team pinpointed genes that affect the cell’s ability to survive and proliferate, how actively a cell produces inflammatory substances, and how aggressively a cell prunes synapses. And because the scientists had determined which genes control those activities, they were able to reset the genes and flip the diseased cell to a healthy state.

Source: https://www.ucsf.edu/

How To Generate Hot Water For Free

The HERU is a world-first global solution that literally gives you the power of generating hot water for your home from everyday items you previously had little option but to discard as waste.

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The patented, micro-scale Home Energy Resources Unit (HERU) is designed to fit seamlessly into the curtilage of your domestic property, changing the life course of most items and materials in your home. It provides a method to keep most household items as a resource by using them to power your boiler, moving you away from a linear approach to consumerism (buy, use, dispose), into a circular one, whereby ‘wastes’ never become. Imagine buying an item, bringing it home, putting the item into use and using the packaging it was wrapped up in to energise your home. The HERU enables you to utilise 100% of most products you buy, without the need to discard anything.

The ground-breaking process is simple to operate, akin to other white goods in the home such as your washing machine or dishwasher. Similarly to other white goods, the HERU requires a water supply, a standard 13-amp electrical power supply and a sewer pipe connection. We synchronise it with your gas or oil boiler so your boiler becomes a hybrid water heating system – meaning it can run via HERU, or revert back to oil or gas as and when needed. The process then uses heat treatment to break materials down and produce an average of 2.5 times the amount of energy used to run the HERU – and all at a standard oven temperature of up to 300°C.

Source: https://www.myheru.com/