3 years ago

Endosomal sorting and trafficking, the retromer complex and neurodegeneration

Endosomal sorting and trafficking, the retromer complex and neurodegeneration
Alana N. Vagnozzi, Domenico Praticò
The retromer is a highly conserved multimeric protein complex present in all eukaryotic cells whose activity is essential for regulating the recycling and retrieval of numerous protein cargos from the endosome to trans-Golgi network or the cell surface. In recent years, molecular and genomic studies have provided evidence that aberrant regulation of endosomal protein sorting and trafficking secondary to a dysfunction of the retromer complex could be implicated in the pathogenesis of several neurodegenerative diseases. Thus, deficiency or mutations in one or more protein components of the retromer leads to increased accumulation of protein aggregates, as well as enhanced cellular neurotoxicity. In this review, we will discuss the structure and function of the retromer complex and its neurobiology, its relevance to key molecules involved in neurodegeneration and the potential role that it plays in the development of two major neurodegenerative disorders, Parkinson’s disease and Alzheimer’s disease. Finally, we will discuss the viability of targeting the retromer via pharmacological chaperones or genetic approaches to enhance or restore its function as a novel and unifying disease-modifying strategy against these diseases.

Publisher URL: https://www.nature.com/articles/s41380-018-0221-3

DOI: 10.1038/s41380-018-0221-3

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.