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7

INSIDE SALK

SUMMER 2016

WWW.SALK.EDU

Salk Institute scientists

showed how an FDA-

approved drug boosts the

health of brain cells by

limiting their energy use.

Like removing unnecessary

lighting from a financially

strapped household to save

on electricity bills, the

drug—called rapamycin—

prolongs the survival of

diseased neurons by forcing

them to reduce protein

production to conserve

cellular energy.

Rapamycin has been shown to extend

lifespan and reduce symptoms in a

broad range of diseases and, at the

cellular level, is known to slow down

the rate at which proteins are made.

But the new Salk research, led by Salk

Professor Tony Hunter and published

in the journal

eLife,

suggests that

rapamycin could also target the

neural damage associated with Leigh

syndrome, a rare genetic disease,

and potentially other forms of

neurodegeneration as well.

Previous studies on rapamycin, which

blocks an energy sensor in cells,

suggested that the drug prevents

neurodegeneration by encouraging

cells to degrade damaged components.

But recent data hinted that rapamycin

might also affect mitochondria,

organelles that produce energy in the

form of adenosine triphosphate (ATP).

Hunter, Salk Professor Rusty Gage, first

author Xinde Zheng and colleagues

reprogrammed skin cells from patients

with Leigh syndrome into brain

cells in a dish. The Leigh syndrome

neurons decayed and showed clear

signs of energy depletion. Meanwhile,

Leigh syndrome neurons exposed to

rapamycin had more ATP and showed

less degeneration. By turning down the

dial on protein production, the diseased

neurons were able to survive longer.

The teams are continuing to investigate

how rapamycin’s effect on reducing

protein synthesis could be harnessed

into a treatment for mitochondria-

related neurodegenerative diseases.

TAMPING DOWN NEURONS’

ENERGY USE COULD TREAT

NEURODEGENERATION

Edward Callaway’s lab has developed a

new reagent to map the brain’s complex

network of connections that is 20 times

more efficient than their previous

version. This tool, detailed by first

author Euiseok Kim in

Cell Reports

in

April 2016, improves upon a technique

called rabies virus tracing, which

was originally developed by Callaway

and is commonly used to map neural

connections.

This dramatic improvement will help

researchers illuminate aspects of brain

disorders where connectivity and global

processing goes awry, such as in autism,

schizophrenia and some motor and

neurodevelopmental diseases.

BRAIN MAPPING

TOOL 20 TIMES

MORE POWERFUL

THAN PREVIOUS

VERSION

In a mouse brain section (thalamus),

neurons providing monosynaptic inputs

to cortical inhibitory neurons are traced via

rabies (blue). Purple counterstaining shows

surrounding cellular architecture.