Tau protein exhibits surprising advantages in mitigating mind harm

A research by researchers at Baylor School of Drugs and the Jan and Dan Duncan Neurological Analysis Institute (Duncan NRI) at Texas Kids’s Hospital, reveals that the protein Tau – a key participant implicated in a number of neurodegenerative circumstances together with Alzheimer’s illness – additionally performs a constructive position within the mind. Tau mitigates neuronal harm attributable to extreme reactive oxygen species (ROS) or free radicals and promotes wholesome ageing. The research was revealed in Nature Neuroscience.

“ROS are pure byproducts of varied mobile capabilities within the physique. Whereas low ranges of ROS are helpful, extra ROS is dangerous to cells because it triggers the manufacturing of poisonous types of different molecules that induce oxidative stress, together with peroxidated lipids,” stated lead writer Dr. Lindsey Goodman, a postdoctoral fellow within the lab of Dr. Hugo Bellen. “Neurons are notably vulnerable to oxidative stress and are destroyed if peroxidated lipid ranges usually are not tightly managed.”

Lipid droplets shield the mind from oxidative harm

There’s mounting proof supporting the notion that our brains have developed a number of neuroprotective methods to fight ROS-induced oxidative harm.

One of many methods, found in 2015 by the Bellen workforce, consists of neurons exporting these poisonous peroxidated lipids to neighboring glial cells, which sequester them into lipid droplets for storage and future vitality manufacturing. “This course of successfully removes and neutralizes these poisonous lipids,” Goodman stated. “Within the present research we investigated the position of Tau within the formation of glial lipid droplets.”

The workforce discovered that endogenous regular Tau in flies is required for glial lipid droplet formation and for shielding in opposition to neuronal ROS. Equally, Tau was required in glial cells obtained from rats and people to kind lipid droplets.

And whereas expression of regular human Tau was adequate to revive the method of formation and maturation of glial lipid droplets in flies missing their very own Tau, when this human Tau protein carried disease-causing mutations – that are linked to an elevated danger for Alzheimer’s illness – the glia have been incapable of forming lipid droplets in response to neuronal ROS.

This argues that mutations in Tau could cut back the protein’s regular capacity to stop oxidative stress along with inflicting the protein to build up into the standard hallmarks of illness, as described by earlier work. Altogether, the findings assist a brand new neuroprotective position for Tau in opposition to the toxicity related to ROS.”

Dr. Lindsey Goodman, lead writer

Additional connections with illness have been found utilizing established fly and rat fashions of Tau-mediated circumstances that overexpress disease-causing human Tau protein in glia. In these eventualities, the investigators once more noticed defects in glial lipid droplets and glial cell demise in response to neuronal ROS. This demonstrated that Tau is a dosage-sensitive regulator of glial lipid droplets the place an excessive amount of or too little Tau is detrimental.

“By revealing a stunning new neuroprotective position for Tau, the research opens the door to potential new methods to gradual, reverse and deal with neurodegenerative circumstances,” stated Bellen, corresponding writer of the work. He’s a distinguished service professor in molecular biology and genetics at Baylor and holds a Chair in Neurogenetics at Duncan NRI. Bellen is also a March of Dimes Professor in Developmental Biology at Baylor.

In abstract, opposite to its normal ‘dangerous man’ position in neurodegenerative illness, this research demonstrates that Tau additionally performs a ‘good man’ position in glia by serving to sequester poisonous lipids, lowering oxidative harm and, therefore defending our brains. Nevertheless, when Tau is absent or when faulty Tau proteins are current, this protecting impact disappears, resulting in illness.