PXD030021

PXD030021 is an original dataset announced via ProteomeXchange.

Title	Neuronal and astrocytic contributions to Huntington’s disease dissected following mutant Huntingtin (mHTT) lowering
Description	Huntington’s disease (HD) is caused by expanded CAG repeats in the Huntingtin gene (HTT) that results in expression of mutant HTT proteins (mHTT) with extended polyglutamine tracts in diverse cells of the body, including striatal neurons and astrocytes. The relative contributions of neurons and astrocytes to disease pathogenesis are unknown for HD and other neurodegenerative diseases. This is a critical issue to address since it has been proposed that neuronal loss in HD and other major neurodegenerative diseases is downstream of astrocytic dysfunction that drives neuronal death. Moreover, astrocyte-to-neuron conversion is considered a promising approach in HD and other neurodegenerative diseases with little reported detriment with regards to normal astrocytic physiological functions, which are varied and extensive in health and disease. Thus, astrocytes are considered both causative and also largely replaceable in neurodegeneration, and their basic contributions to disease pathophysiology relative to neurons remain undefined in vivo. We used genetically encoded and cell-specific zinc finger protein (ZFP) transcriptional repressors to lower mHTT and molecularly dissected neuronal and astrocytic influences on HD pathophysiology at molecular, cellular, and behavioral levels. We found that the major disease drivers were in fact neurons, with astrocytes displaying lesser loss of essential functions such as cholesterol metabolism that were downstream of greater neuronal dysfunction, which encompassed neuromodulation, synaptic, and intracellular signaling. We thus dissected the cell autonomous and non-cell autonomous mechanistic and causal contributions of both neurons and astrocytes to a complex neurodegenerative disease in vivo with wider implications for rescue and repair strategies.
HostingRepository	PRIDE
AnnounceDate	2022-12-15
AnnouncementXML	Submission_2022-12-14_17:52:55.783.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	YasamanJami-Alahmadi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-28 14:16:22	ID requested
⏵ 1	2022-12-14 17:52:56	announced

Dataset with its publication pending

submitter keyword: proteomics,Huntington disease , mass spectrometry,cholesterol metabolism,intracellular signaling,Neuronal and astrocyte, mHTT

Baljit S.Khakh
contact affiliation	Department of Physiology, Department of Neurobiology, University of California Los Angeles. Los Angeles, CA 90095-1751, USA
contact email	BKhakh@mednet.ucla.edu
lab head
YasamanJami-Alahmadi
contact affiliation	UCLA
contact email	yjami@ucla.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/12/PXD030021

PRIDE project URI

• PRIDE
  1. PXD030021
     1. Label: PRIDE project
     2. Name: Neuronal and astrocytic contributions to Huntington’s disease dissected following mutant Huntingtin (mHTT) lowering