Recent findings in the understanding of amyotrophic lateral sclerosis (ALS) revealed that alteration in calcium (Ca2+) homeostasis may largely contribute to motor neuron demise. A large part of these alterations is due to dysfunctional Ca2+-storing organelles, including the endoplasmic reticulum (ER) and mitochondria. Very recently, lysosomal Ca2+ dysfunction has emerged as an important pathological change leading to neuronal loss in ALS. Remarkably, the Ca2+-storing organelles are interacting with each other at specialized domains controlling mitochondrial dynamics, ER/lysosomal function, and autophagy. This occurs as a result of interaction between specific ionic channels and Ca2+-dependent proteins located in each structure. Therefore, the dysregulation of these ionic mechanisms could be considered as a key element in the neurodegenerative process. This review will focus on the possible role of lysosomal Ca2+ dysfunction in the pathogenesis of several neurodegenerative diseases, including ALS and shed light on the possibility that specific lysosomal Ca2+ channels might represent new promising targets for preventing or at least delaying neurodegeneration in ALS.

Calcium Dyshomeostasis and Lysosomal Ca2+ Dysfunction in Amyotrophic Lateral Sclerosis / Tedeschi, Valentina; Petrozziello, Tiziana; Secondo, Agnese. - In: CELLS. - ISSN 2073-4409. - 8:10(2019), p. 1216. [10.3390/cells8101216]

Calcium Dyshomeostasis and Lysosomal Ca2+ Dysfunction in Amyotrophic Lateral Sclerosis

Secondo, Agnese
2019-01-01

Abstract

Recent findings in the understanding of amyotrophic lateral sclerosis (ALS) revealed that alteration in calcium (Ca2+) homeostasis may largely contribute to motor neuron demise. A large part of these alterations is due to dysfunctional Ca2+-storing organelles, including the endoplasmic reticulum (ER) and mitochondria. Very recently, lysosomal Ca2+ dysfunction has emerged as an important pathological change leading to neuronal loss in ALS. Remarkably, the Ca2+-storing organelles are interacting with each other at specialized domains controlling mitochondrial dynamics, ER/lysosomal function, and autophagy. This occurs as a result of interaction between specific ionic channels and Ca2+-dependent proteins located in each structure. Therefore, the dysregulation of these ionic mechanisms could be considered as a key element in the neurodegenerative process. This review will focus on the possible role of lysosomal Ca2+ dysfunction in the pathogenesis of several neurodegenerative diseases, including ALS and shed light on the possibility that specific lysosomal Ca2+ channels might represent new promising targets for preventing or at least delaying neurodegeneration in ALS.
2019
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/337756
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 33
  • ???jsp.display-item.citation.isi??? 28
social impact