Neuronal
loss/destruction is the leading cause of symptoms in patients suffering from
neural injury or neurodegenerative disorders.
Following neural insult
astrocytes proliferate and become active glial cells to form glial scarring in
order to protect neighboring tissue from further damage.
The downside to this
scarring is the inhibition of neuronal growth and synaptic transmission which
would allow for the recovery following the insults mentioned above.
Recent
research from Penn State University has resulted in a protocol involving four
small molecules that together can efficiently program astrocytes into fully
fuctional nerons. In vitro SB431542 5 micromolar, LDN193189 0.25 micromolar,
CHIR99021 1.5 micomolar and DAPT 0.25 micromolar added to astrocytes led over
six days to a neuronal yield (converted neurons/astrocyte) of 71%!
Furthermore
the drug converted human neurons could survive 3-7 months in culture and form
robust synaptic connections.
Even more impressive is the in vivo obsevations
that intracranial injection in to the mouse hippocampus or intraperitoneal
injections over three weeks both yielded significant neurogenesis. The data
from the IP injection suggests that the molecules cross the mouse blood brain
barrier and with some suitable medicinal chemistry these compounds could be
formulated and administered IP or even orally for the treatment of such
diseases as stroke, Dementia or spinal injury.
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