ALS lymphoblastoid cell lines as a considerable model to understand disease mechanisms

O Pansarasa, M Bordoni, L Dufruca, L Diamanti, D Sproviero, R Trotti, S Bernuzzi, S La Salvia, S Gagliardi, M Ceroni, C Cereda

Research output: Contribution to journalArticle

Abstract

New evidences switch the hypothesis of amyotrophic lateral sclerosis (ALS) from a "neurocentric" to a "multisystemic" or "non-neurocentric" point of view. From 2006, we focused on the study of non-neural cells, patients' peripheral blood mononuclear cells (PMBCs) and lymphoblastoid cell lines (LCLs). Here, we characterized LCLs of sporadic ALS and patients carrying SOD1, TARDBP and FUS mutations to identify ALS biologically relevant signature, and whether and how mutations differentially affect ALS-linked pathways. Although LCLs are different from motor neurons (MNs), in LCLs we find out some features typical of degenerating MNs in ALS, i.e. protein aggregation and mitochondrial dysfunction. Moreover, different gene mutations otherwise affect ALS cellular mechanisms. TARDBP and FUS mutations imbalance mitochondrial dynamism toward an increased fusion, while sALS and SOD1 mutations mainly affect fission. As regard protein aggregation and/or mislocalization, TARDBP and SOD1 mutations show the presence of aggregates, while FUS mutation does not induce protein aggregation and/or mislocalization. Finally, all LCLs, independently from mutation, are not able to work in a condition of excessive energy request, suggesting that mitochondria from ALS patients are characterized by a significant metabolic defect. Taken together these data indicate that LCLs could be indicated as a valid cellular model in ALS research to study specific pathological pathways or to identify new ones.

Original languageEnglish
JournalDMM Disease Models and Mechanisms
DOIs
Publication statusE-pub ahead of print - Jan 29 2018

Fingerprint

Amyotrophic Lateral Sclerosis
Agglomeration
Cells
Cell Line
Mutation
Neurons
Proteins
Mitochondria
Motor Neurons
Blood
Fusion reactions
Genes
Switches
Defects
Mitochondrial Proteins
Blood Cells
Research

Keywords

  • Journal Article

Cite this

ALS lymphoblastoid cell lines as a considerable model to understand disease mechanisms. / Pansarasa, O; Bordoni, M; Dufruca, L; Diamanti, L; Sproviero, D; Trotti, R; Bernuzzi, S; La Salvia, S; Gagliardi, S; Ceroni, M; Cereda, C.

In: DMM Disease Models and Mechanisms, 29.01.2018.

Research output: Contribution to journalArticle

@article{1cc335088c8046409bf965ffc3210615,
title = "ALS lymphoblastoid cell lines as a considerable model to understand disease mechanisms",
abstract = "New evidences switch the hypothesis of amyotrophic lateral sclerosis (ALS) from a {"}neurocentric{"} to a {"}multisystemic{"} or {"}non-neurocentric{"} point of view. From 2006, we focused on the study of non-neural cells, patients' peripheral blood mononuclear cells (PMBCs) and lymphoblastoid cell lines (LCLs). Here, we characterized LCLs of sporadic ALS and patients carrying SOD1, TARDBP and FUS mutations to identify ALS biologically relevant signature, and whether and how mutations differentially affect ALS-linked pathways. Although LCLs are different from motor neurons (MNs), in LCLs we find out some features typical of degenerating MNs in ALS, i.e. protein aggregation and mitochondrial dysfunction. Moreover, different gene mutations otherwise affect ALS cellular mechanisms. TARDBP and FUS mutations imbalance mitochondrial dynamism toward an increased fusion, while sALS and SOD1 mutations mainly affect fission. As regard protein aggregation and/or mislocalization, TARDBP and SOD1 mutations show the presence of aggregates, while FUS mutation does not induce protein aggregation and/or mislocalization. Finally, all LCLs, independently from mutation, are not able to work in a condition of excessive energy request, suggesting that mitochondria from ALS patients are characterized by a significant metabolic defect. Taken together these data indicate that LCLs could be indicated as a valid cellular model in ALS research to study specific pathological pathways or to identify new ones.",
keywords = "Journal Article",
author = "O Pansarasa and M Bordoni and L Dufruca and L Diamanti and D Sproviero and R Trotti and S Bernuzzi and {La Salvia}, S and S Gagliardi and M Ceroni and C Cereda",
note = "{\circledC} 2018. Published by The Company of Biologists Ltd.",
year = "2018",
month = "1",
day = "29",
doi = "10.1242/dmm.031625",
language = "English",
journal = "DMM Disease Models and Mechanisms",
issn = "1754-8403",
publisher = "Company of Biologists Ltd",

}

TY - JOUR

T1 - ALS lymphoblastoid cell lines as a considerable model to understand disease mechanisms

AU - Pansarasa, O

AU - Bordoni, M

AU - Dufruca, L

AU - Diamanti, L

AU - Sproviero, D

AU - Trotti, R

AU - Bernuzzi, S

AU - La Salvia, S

AU - Gagliardi, S

AU - Ceroni, M

AU - Cereda, C

N1 - © 2018. Published by The Company of Biologists Ltd.

PY - 2018/1/29

Y1 - 2018/1/29

N2 - New evidences switch the hypothesis of amyotrophic lateral sclerosis (ALS) from a "neurocentric" to a "multisystemic" or "non-neurocentric" point of view. From 2006, we focused on the study of non-neural cells, patients' peripheral blood mononuclear cells (PMBCs) and lymphoblastoid cell lines (LCLs). Here, we characterized LCLs of sporadic ALS and patients carrying SOD1, TARDBP and FUS mutations to identify ALS biologically relevant signature, and whether and how mutations differentially affect ALS-linked pathways. Although LCLs are different from motor neurons (MNs), in LCLs we find out some features typical of degenerating MNs in ALS, i.e. protein aggregation and mitochondrial dysfunction. Moreover, different gene mutations otherwise affect ALS cellular mechanisms. TARDBP and FUS mutations imbalance mitochondrial dynamism toward an increased fusion, while sALS and SOD1 mutations mainly affect fission. As regard protein aggregation and/or mislocalization, TARDBP and SOD1 mutations show the presence of aggregates, while FUS mutation does not induce protein aggregation and/or mislocalization. Finally, all LCLs, independently from mutation, are not able to work in a condition of excessive energy request, suggesting that mitochondria from ALS patients are characterized by a significant metabolic defect. Taken together these data indicate that LCLs could be indicated as a valid cellular model in ALS research to study specific pathological pathways or to identify new ones.

AB - New evidences switch the hypothesis of amyotrophic lateral sclerosis (ALS) from a "neurocentric" to a "multisystemic" or "non-neurocentric" point of view. From 2006, we focused on the study of non-neural cells, patients' peripheral blood mononuclear cells (PMBCs) and lymphoblastoid cell lines (LCLs). Here, we characterized LCLs of sporadic ALS and patients carrying SOD1, TARDBP and FUS mutations to identify ALS biologically relevant signature, and whether and how mutations differentially affect ALS-linked pathways. Although LCLs are different from motor neurons (MNs), in LCLs we find out some features typical of degenerating MNs in ALS, i.e. protein aggregation and mitochondrial dysfunction. Moreover, different gene mutations otherwise affect ALS cellular mechanisms. TARDBP and FUS mutations imbalance mitochondrial dynamism toward an increased fusion, while sALS and SOD1 mutations mainly affect fission. As regard protein aggregation and/or mislocalization, TARDBP and SOD1 mutations show the presence of aggregates, while FUS mutation does not induce protein aggregation and/or mislocalization. Finally, all LCLs, independently from mutation, are not able to work in a condition of excessive energy request, suggesting that mitochondria from ALS patients are characterized by a significant metabolic defect. Taken together these data indicate that LCLs could be indicated as a valid cellular model in ALS research to study specific pathological pathways or to identify new ones.

KW - Journal Article

U2 - 10.1242/dmm.031625

DO - 10.1242/dmm.031625

M3 - Article

JO - DMM Disease Models and Mechanisms

JF - DMM Disease Models and Mechanisms

SN - 1754-8403

ER -