Synapses, Parkinson's Disease, & NCL - The Chandra Lab at Yale School of Medicine

Transcript

• 00:06The human brain has
• 00:08over a hundred trillion
• 00:10synapses.
• 00:12They're sort of the communication
• 00:14hub of the neuron.
• 00:15Any given neuron
• 00:17may have an electrical signal
• 00:19that goes down and then
• 00:20it releases neurotransmitters
• 00:22and those neurotransmitters are kind
• 00:24of like the messengers for
• 00:25that neuron that then gets
• 00:26sent to whatever neuron it
• 00:28is synapsing with and then
• 00:29that propagates the signal.
• 00:31Strengthening synapses and pruning synapses
• 00:34to make specific new connections
• 00:37between different parts of your
• 00:38brain. It allows the neurons
• 00:39to form into neurocircuits,
• 00:41which then pretty much controls
• 00:43every aspect of our brain
• 00:44and body functions. No other
• 00:45cell really communicates like neurons
• 00:48do, and it's an integral
• 00:50portion of not only their
• 00:52identity,
• 00:53but their function. You get
• 00:54rid of the synapse, you
• 00:55start to lose neurons.
• 01:02Any
• 01:03neurological disease
• 01:04is gonna mess up the
• 01:05synapse somehow.
• 01:08Neurodegenerative
• 01:09disease is characterized by loss
• 01:11of neurons, but what happens
• 01:13prior to the deaths of
• 01:13the neurons is that actually
• 01:15the synapses
• 01:16become dysfunctional first. Synapses are
• 01:19starting to be
• 01:21recognized as an early site
• 01:22of pathology and neurodegenerative
• 01:24diseases.
• 01:25And in these diseases,
• 01:27there's a long silent phase
• 01:30where the disease processes are
• 01:32already ongoing, but the patient
• 01:35or the person has no
• 01:36obvious
• 01:37symptoms. So our focus of
• 01:39the lab is exactly that,
• 01:40to understand
• 01:41synaptic biology in the context
• 01:44of neurodegeneration.
• 01:45And there, we study synuclein,
• 01:48which is a protein that's
• 01:49found at the synapse and
• 01:51linked causally to disease.
• 02:01We have people trying to
• 02:02understand different
• 02:04confirmations
• 02:05and structures of synuclein in
• 02:07the different synucleinopathies.
• 02:09We're also interested in
• 02:12a genetically related
• 02:13disease, which is interestingly also
• 02:16involved at the synapse where
• 02:18this key protein called cysteine
• 02:20string alpha protein
• 02:23is
• 02:23involved in this rare children's
• 02:26disease.
• 02:27And it's also involved in
• 02:29lysosomal function. And we're really
• 02:31interested in actually knowing to
• 02:33what extent does the lysosome
• 02:36play
• 02:37in maintaining a synapse, and
• 02:39is that maybe replicated across
• 02:41other neurodegenerative diseases?
• 02:43My research is specifically looking
• 02:45at the gut brain connection
• 02:47in Parkinson's.
• 02:48How alpha synuclein and this,
• 02:50you know, synaptic dysfunction
• 02:52might be happening first in
• 02:54the neurons that are actually
• 02:55in your gut.
• 02:57I am interested in aging
• 02:59as a risk factor for
• 03:01neurodegeneration.
• 03:02That's a lipid modification on
• 03:04proteins that we know accumulates
• 03:06with age, and it affects
• 03:08how proteins localize and function.
• 03:11We also do a lot
• 03:12of imaging to look at
• 03:13localization
• 03:14and expression of proteins. I
• 03:16actually isolate a dopaminergic
• 03:17rich area of the brain
• 03:18and culture dopaminergic neurons from
• 03:21mice and then do, like,
• 03:22live imaging and different assays.
• 03:24My project's specific focus is
• 03:26on whether and how microglia
• 03:28contribute to the early synapse
• 03:29loss in Parkinson's disease. We
• 03:31use both,
• 03:32genetic and induced mouse models
• 03:34because Parkinson's disease patients can
• 03:37be both sporadic or genetically
• 03:39inherited.
• 03:40So by comparing the mechanisms
• 03:42between the genetic and used
• 03:43mouse models, I hope to
• 03:45find a general microglia synapse
• 03:47interaction
• 03:48pathway that's applicable
• 03:50to all the disease patients.
• 03:58What motivates me to do
• 04:00this research is knowing that
• 04:01if we do and when
• 04:03we do find something
• 04:05that causes this synapse dysfunction,
• 04:07being able to get that
• 04:08translated into some sort of
• 04:10therapeutic.
• 04:12So we can do so
• 04:13much with this research to
• 04:15open up doors for clinical
• 04:16trials and improve the quality
• 04:18of life for people around
• 04:20the world.