Role of endolysosomes and inter-organellar signaling in brain disease

NEUROBIOLOGY OF DISEASE

卷:134

Review

Afghah, Zahra¹  Chen, Xuesong¹  Geiger, Jonathan D.¹ 

[1] Univ North Dakota, Sch Med & Hlth Sci, Dept Biomed Sci, 504 Hamline St,Room 110, Grand Forks, ND 58201 USA

关键词: Endolysosomes;    Mitochondria;    Endoplasmic reticulum;    Plasma membranes;    Calcium;    Neurodegenerative diseases;    HIV-1 associated neurocognitive disorder;    Alzheimer's disease;    Glioblastoma multiforme;    Parkinson's disease;   

DOI  :  10.1016/j.nbd.2019.104670

来源: Elsevier

【 摘 要 】

Endosomes and lysosomes (endolysosomes) are membrane bounded organelles that play a key role in cell survival and cell death. These acidic intracellular organelles are the principal sites for intracellular hydrolytic activity required for the maintenance of cellular homeostasis. Endolysosomes are involved in the degradation of plasma membrane components, extracellular macromolecules as well as intracellular macromolecules and cellular fragments. Understanding the physiological significance and pathological relevance of endolysosomes is now complicated by relatively recent findings of physical and functional interactions between endolysosomes with other intracellular organelles including endoplasmic reticulum, mitochondria, plasma membranes, and peroxisomes. Indeed, evidence clearly indicates that endolysosome dysfunction and inter-organellar signaling occurs in different neurodegenerative diseases including Alzheimer's disease (AD), HIV-1 associated neurocognitive disease (HAND), Parkinson's disease (PD) as well as various forms of brain cancer such as glioblastoma multiforme (GBM). These findings open new areas of cell biology research focusing on understanding the physiological actions and pathophysiological consequences of inter-organellar communication. Here, we will review findings of others and us that endolysosome de-acidification and dysfunction coupled with impaired inter-organellar signaling is involved in the pathogenesis of AD, HAND, PD, and GBM. A more comprehensive appreciation of cell biology and inter-organellar signaling could lead to the development of new drugs to prevent or cure these diseases.