The Golgi Apparatus: A Voyage through Time, Structure, Function and Implication in Neurodegenerative Disorders

Abstract

This comprehensive review article dives deep into the Golgi apparatus, an essential organelle in cellular biology. Beginning with its discovery during the 19th century until today’s recognition as an important contributor to cell function. We explore its unique organization and structure as well as its roles in protein processing, sorting, and lipid biogenesis, which play key roles in maintaining homeostasis in cellular biology. This article further explores Golgi biogenesis, exploring its intricate processes and dynamics that contribute to its formation and function. One key focus is its role in neurodegenerative diseases like Parkinson’s, where changes to the structure or function of the Golgi apparatus may lead to their onset or progression, emphasizing its key importance in neuronal health. At the same time, we examine the intriguing relationship between Golgi stress and endoplasmic reticulum (ER) stress, providing insights into their interplay as two major cellular stress response pathways. Such interdependence provides a greater understanding of cellular reactions to protein misfolding and accumulation, hallmark features of many neurodegenerative diseases. In summary, this review offers an exhaustive examination of the Golgi apparatus, from its historical background to its role in health and disease. Additionally, this examination emphasizes the necessity of further research in this field in order to develop targeted therapeutic approaches for Golgi dysfunction-associated conditions. Furthermore, its exploration is an example of scientific progress while simultaneously offering hope for developing innovative treatments for neurodegenerative disorders.

Modulating Golgi Stress Signaling Ameliorates Cell Morphological Phenotypes Induced by CHMP2B with Frontotemporal Dementia-Associated p.Asp148Tyr

“…Accumulating reports have begun to classify the molecules responsible for Golgi stress into several pathways [35][36][37][38][39][40]. It is likely that Golgi stress is mediated by three major pathways through (1) an unidentified transcription factor and its possible downstream target, Hsp47, with a role in protecting cells; (2) the cAMP-responsive element binding protein 3 (CREB3) transcription factor and its downstream target, Arf4; and (3) transcription factor E3 (TFE3) and downstream targets such as the structural proteins composing the Golgi body, for example, GM130 [35][36][37][38][39][40]. It is believed that Hsp47 often composes an anti-apoptotic pathway in cell types such as fibroblasts [41,42], whereas signaling through CREB3 composes a pro-apoptotic, pre-apoptotic, and/or apoptotic pathway [43,44].…”

“…The Golgi stress pathway is thought to mediate the effects of some specific stresses within mammalian cells. Like the unfolded protein response (UPR) in ERs, part of these pathways is related to arresting the cell cycle, at least in fibroblasts [27]; however, the roles of Golgi stress responses in many other types of cells remain unclear [35][36][37][38][39][40].…”

“…Thus, we tested the possibility that mutated CHMP2B triggers organelle stress in the Golgi body. The molecular pathways associated with Golgi stress primarily involve those through (1) Hsp47 (also called serpin family H member 1 [SerpinH1]), (2) Arf4, and (3) structural proteins composing the Golgi body, such as GM130 [35][36][37][38][39][40]. Proteins such as Hsp47 and GM130 have protective effects on Golgi and cell homeostasis; in contrast, proteins such as Arf4 likely function as alarm-like molecules for Golgi stress [41][42][43][44][45][46].…”

“…In addition, the knockdown of Arf4 recovered phenotypes in cells harboring mutated CHMP2B (Figure 4B). Although there is no consensus regarding all Golgi stress-signaling pathways [39][40][41][42][43][44], it is known that flavonoids such as hesperetin can reduce this stress through various Golgi stress-signaling pathways, including Hsp47, Arf4, and Golgi body structural proteins [35][36][37][38][39][40]. To further reconfirm that reducing Golgi stress can recover mutated CHMP2B-induced phenotypes in cells, we investigated whether hesperetin, serving as a positive control chemical, has a protective effect on cells harboring mutated CHMP2B.…”