This website uses cookies so that we can provide you with the best user experience possible. Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful.
Catalog
ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
Article
Proteostasis and lysosomal quality control deficits in Alzheimer’s disease neurons
Compounds enhancing lysosomal function broadly ameliorate AD-associated pathologies. The authors’ findings establish cell-autonomous LQC dysfunction in neurons as a central vulnerability in aging and AD pathogenesis.
Teams
Themes
Article
Proteome census upon nutrient stress reveals Golgiphagy membrane receptors
During nutrient stress, macroautophagy is employed to degrade cellular macromolecules, thereby providing biosynthetic building blocks while simultaneously remodeling the proteome. The authors’ results, available via an interactive web tool, reveal that autophagic turnover prioritizes membrane-bound organelles (principally Golgi and ER) for proteome remodeling during nutrient stress.
Teams
Themes
Article
UniProtExtractR: an app and R package for easily extracting protein-specific UniProtKB information and fine-tuning organelle resolution
The app features interactive frequency tables that globally summarize both the original UniProtKB input query as well as the extracted/changed entry values. Moreover, UniProtExtractR includes a tractable mapping algorithm to define custom organelle-level resolution.
Teams
Themes
Article
Mechanism of human PINK1 activation at the TOM complex in a reconstituted system
Preprint: The authors demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These molecular findings will aid in the development of small molecule activators of PINK1 as a therapeutic strategy for PD.
Article
Autophagy preferentially degrades non-fibrillar polyQ aggregates
Preprint: These results suggest that the limited efficiency of autophagy in clearing polyQ aggregates is due to the inability of autophagosomes to interact productively with the non-deformable, fibrillar disease aggregates.
Teams
Themes
Article
Visualizing chaperone-mediated multistep assembly of the human 20S proteasome
Dedicated assembly factors orchestrate the stepwise production of molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. This article presents cryo-EM reconstructions of seven recombinant human subcomplexes that visualize all five chaperones and the three active site propeptides across a wide swath of the assembly pathway.
Teams
Themes
Article
Global ubiquitylation analysis of mitochondria in primary neurons identifies endogenous Parkin targets following activation of PINK1
Published: Loss-of-function mutations in Parkin cause disruption of mitophagy and are associated with PD. Yet, much of the biology surrounding Parkin function has taken place in artificial cell systems. The authors used human neurons to identify and validate 22 protein targets of Parkin, providing a functional Parkin landscape in neuronal cells.
Themes
Article
Global ubiquitylation analysis of mitochondria in primary neurons identifies physiological Parkin targets following activation of PINK1
Published: Mutations in PINK1 and Parkin are implicated in PD via abherrant mitophagy. The authors identified ubiquitylated substrates of endogenous Parkin in mouse neurons by proteomic analysis. They identified and validated 22 protein targets of Parkin that are conserved in human neurons providing a functional Parkin landscape in neuronal cells. View original preprint.
Themes
Article
Spatial snapshots of amyloid precursor protein intramembrane processing via early endosome proteomics
Published: The authors developed an assay, Endo-IP, to rapidly isolate early and sorting endosomes. Using this method, they found a unique proteomic landscape of early/sorting endosomes, distinct from lysosomal proteomic landscape. Combining Endo-IP and Lyso-IP, the authors provided a spatial digital snapshot of amyloid-beta products. View original preprint.
Teams
Themes
Article
In situ structural analysis reveals membrane shape transitions during autophagosome formation
Preprint: A hallmark of PD is the failure of quality control mechanisms in the cell, such as autophagy. The authors combined cell biology with correlative cryo-electron tomography in yeast cells to show a high resolution stepwise structural progression of autophagosome biogenesis. Further, they revealed the organelle interactome for growing autophagosomes.
Themes
Article
The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends
Published: Irreversible toxic aggregates are a hallmark of neurodegenerative diseases, such as alpha-synuclein in PD. Using microfluidic diffusional sizing, the authors show that the molecular chaperone family Hsp70 (specifically Hsc70, DnaJB, and Apg2) can completely dissolve alpha-synuclein aggregation and revert it back to its monomeric state.
Teams
Themes
Article
In situ architecture of neuronal α-Synuclein inclusions
Published: Alpha-synuclein aggregation has been associated with Parkinson’s disease. Using cutting-edge imaging tools, the authors show neuronal alpha-synuclein inclusions within their native states. Further, they show that these aggregates are intermixed with cellular organelles and how aggregation spreads across the brain. View original preprint.
Teams
Themes
Article
Quantitative proteomics reveals the selectivity of ubiquitin-binding autophagy receptors in the turnover of damaged lysosomes by lysophagy
Published: The authors used proteomics to develop a quantitative snapshot of the proteins involved in lysophagy. Among the proteins identified, they found that TAX1BP1 and TBK1 are both required for lysophagy. View original preprint.
Teams
Themes
Article
The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model
Published: Tau neuronal aggregation is a driver of some neurodegenerative disorders. These toxic aggregates form when affected cells release aggregate seeds which are then internalized by unaffected cells. The authors show that a protein,Clusterin, delays Tau aggregation and suppresses seeding activity. View original preprint.
Teams
Themes