Preprint Communication Version 2 Preserved in Portico This version is not peer-reviewed

Pioneering Organelle Structural Biology: Golgi Apparatus Dysfunction in Parkinson’s Disease, Neurodevelopmental Disorders, and Cancer

Version 1 : Received: 22 October 2022 / Approved: 25 October 2022 / Online: 25 October 2022 (08:48:38 CEST)
Version 2 : Received: 3 December 2022 / Approved: 5 December 2022 / Online: 5 December 2022 (02:27:26 CET)

How to cite: Gómez, D. Pioneering Organelle Structural Biology: Golgi Apparatus Dysfunction in Parkinson’s Disease, Neurodevelopmental Disorders, and Cancer. Preprints 2022, 2022100383. https://doi.org/10.20944/preprints202210.0383.v2 Gómez, D. Pioneering Organelle Structural Biology: Golgi Apparatus Dysfunction in Parkinson’s Disease, Neurodevelopmental Disorders, and Cancer. Preprints 2022, 2022100383. https://doi.org/10.20944/preprints202210.0383.v2

Abstract

The Golgi apparatus (GA) dysfunctions in Parkinson’s Disease (PD), neurodevelopmental disorders (NDDs), cancer, and organelle structural biology (OSB) can provide insights into therapeutic targets, gene therapy, and drug design. Primary defects and fragmentation within the GA are implicated in a wide range of neurodegenerative diseases. GA defects typically result in mislocation of proteins, accumulation of undegraded proteins, and impaired glycosylation of proteins. Inhibition of vesicular trafficking by α-synuclein (aSyn) may affect the dopamine-producing neurons and neuromodulators. GA regulates apoptosis during pathological mechanisms of neurological diseases and could provide new avenues in treatments through translation research. PD patients bearing the hereditary E46K disease mutation manifest the clinical picture of parkinsonism. How do we provide high resolution nanoimages of the GA during disease to capture dysfunction? Could we visualize the aSyn traffic jam between vesicles in the organelles ER and GA? OSB is emerging as a field as more technology advances and is more accessible. Structural studies of the GA will advance the field of neurological disease forward with an in depth understanding of dysfunction, fragmentation, and defects. Discoveries of the GA in PD, NDDs, and cancer would break new ground and provide translational medicine data of these diseases. Future research could be visualizing high angle annular dark field-STEM (HAADF-STEM) tomograms, cryogenic electron tomography (cryo-ET), multiplex correlative light and electron microscopy (cryo-CLEM), nanobody-assisted tissue immunostaining for volumetric EM (NATIVE) and using soft X-ray tomography (SXT) and computational reconstruction of the GA.

Keywords

structural biology; organelles; Golgi Apparatus (GA); Parkinson’s disease (PD); cryo-ET; alpha-synuclein; neurodegenerative diseases; soft X-ray tomography (SXT); cancer; NDDs

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Comments (1)

Comment 1
Received: 5 December 2022
Commenter: Daniel Gómez-Santos
Commenter's Conflict of Interests: Author
Comment: Figure 2, 3, 4, 5 added

All references to the Golgi apparatus (GA) have been changed to GA that was previously Golgi complex (GA). It may also be referred to as the Golgi body.
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