Molecular Mechanisms Linking ALS/FTD and Psychiatric Disorders, the Potential Effects of Lithium

Fiona Limanaqi, Francesca Biagioni, Larisa Ryskalin, Carla L Busceti, Francesco Fornai

Research output: Contribution to journalReview article

Abstract

Altered proteostasis, endoplasmic reticulum (ER) stress, abnormal unfolded protein response (UPR), mitochondrial dysfunction and autophagy impairment are interconnected events, which contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). In recent years, the mood stabilizer lithium was shown to potentially modify ALS/FTD beyond mood disorder-related pathology. The effects of lithium are significant in ALS patients carrying genetic variations in the UNC13 presynaptic protein, which occur in ALS/FTD and psychiatric disorders as well. In the brain, lithium modulates a number of biochemical pathways involved in synaptic plasticity, proteostasis, and neuronal survival. By targeting UPR-related events, namely ER stress, excitotoxicity and autophagy dysfunction, lithium produces plastic effects. These are likely to relate to neuroprotection, which was postulated for mood and motor neuron disorders. In the present manuscript, we try to identify and discuss potential mechanisms through which lithium copes concomitantly with ER stress, UPR and autophagy dysfunctions related to UNC13 synaptic alterations and aberrant RNA and protein processing. This may serve as a paradigm to provide novel insights into the neurobiology of ALS/FTD featuring early psychiatric disturbances.

Original languageEnglish
Pages (from-to)450
JournalFrontiers in Cellular Neuroscience
Volume13
DOIs
Publication statusPublished - 2019

Cite this

@article{a05d149d9c5e45d998165f0f0ad036cb,
title = "Molecular Mechanisms Linking ALS/FTD and Psychiatric Disorders, the Potential Effects of Lithium",
abstract = "Altered proteostasis, endoplasmic reticulum (ER) stress, abnormal unfolded protein response (UPR), mitochondrial dysfunction and autophagy impairment are interconnected events, which contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). In recent years, the mood stabilizer lithium was shown to potentially modify ALS/FTD beyond mood disorder-related pathology. The effects of lithium are significant in ALS patients carrying genetic variations in the UNC13 presynaptic protein, which occur in ALS/FTD and psychiatric disorders as well. In the brain, lithium modulates a number of biochemical pathways involved in synaptic plasticity, proteostasis, and neuronal survival. By targeting UPR-related events, namely ER stress, excitotoxicity and autophagy dysfunction, lithium produces plastic effects. These are likely to relate to neuroprotection, which was postulated for mood and motor neuron disorders. In the present manuscript, we try to identify and discuss potential mechanisms through which lithium copes concomitantly with ER stress, UPR and autophagy dysfunctions related to UNC13 synaptic alterations and aberrant RNA and protein processing. This may serve as a paradigm to provide novel insights into the neurobiology of ALS/FTD featuring early psychiatric disturbances.",
author = "Fiona Limanaqi and Francesca Biagioni and Larisa Ryskalin and Busceti, {Carla L} and Francesco Fornai",
note = "Copyright {\circledC} 2019 Limanaqi, Biagioni, Ryskalin, Busceti and Fornai.",
year = "2019",
doi = "10.3389/fncel.2019.00450",
language = "English",
volume = "13",
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T1 - Molecular Mechanisms Linking ALS/FTD and Psychiatric Disorders, the Potential Effects of Lithium

AU - Limanaqi, Fiona

AU - Biagioni, Francesca

AU - Ryskalin, Larisa

AU - Busceti, Carla L

AU - Fornai, Francesco

N1 - Copyright © 2019 Limanaqi, Biagioni, Ryskalin, Busceti and Fornai.

PY - 2019

Y1 - 2019

N2 - Altered proteostasis, endoplasmic reticulum (ER) stress, abnormal unfolded protein response (UPR), mitochondrial dysfunction and autophagy impairment are interconnected events, which contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). In recent years, the mood stabilizer lithium was shown to potentially modify ALS/FTD beyond mood disorder-related pathology. The effects of lithium are significant in ALS patients carrying genetic variations in the UNC13 presynaptic protein, which occur in ALS/FTD and psychiatric disorders as well. In the brain, lithium modulates a number of biochemical pathways involved in synaptic plasticity, proteostasis, and neuronal survival. By targeting UPR-related events, namely ER stress, excitotoxicity and autophagy dysfunction, lithium produces plastic effects. These are likely to relate to neuroprotection, which was postulated for mood and motor neuron disorders. In the present manuscript, we try to identify and discuss potential mechanisms through which lithium copes concomitantly with ER stress, UPR and autophagy dysfunctions related to UNC13 synaptic alterations and aberrant RNA and protein processing. This may serve as a paradigm to provide novel insights into the neurobiology of ALS/FTD featuring early psychiatric disturbances.

AB - Altered proteostasis, endoplasmic reticulum (ER) stress, abnormal unfolded protein response (UPR), mitochondrial dysfunction and autophagy impairment are interconnected events, which contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). In recent years, the mood stabilizer lithium was shown to potentially modify ALS/FTD beyond mood disorder-related pathology. The effects of lithium are significant in ALS patients carrying genetic variations in the UNC13 presynaptic protein, which occur in ALS/FTD and psychiatric disorders as well. In the brain, lithium modulates a number of biochemical pathways involved in synaptic plasticity, proteostasis, and neuronal survival. By targeting UPR-related events, namely ER stress, excitotoxicity and autophagy dysfunction, lithium produces plastic effects. These are likely to relate to neuroprotection, which was postulated for mood and motor neuron disorders. In the present manuscript, we try to identify and discuss potential mechanisms through which lithium copes concomitantly with ER stress, UPR and autophagy dysfunctions related to UNC13 synaptic alterations and aberrant RNA and protein processing. This may serve as a paradigm to provide novel insights into the neurobiology of ALS/FTD featuring early psychiatric disturbances.

U2 - 10.3389/fncel.2019.00450

DO - 10.3389/fncel.2019.00450

M3 - Review article

C2 - 31680867

VL - 13

SP - 450

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

SN - 1662-5102

ER -