Research articles

Lighting Up Mislocalized Proteins: Quantum Dot Probes for Multiplexed Cytoplasm-Selective Cell Profiling in Neurodegeneration

Semiconductor quantum dots (QDs) provide unique stability, brightness, and multiplexed capacity for biomarker detection in complex diseases; however, ... Read more...

RNA-binding protein IMP1/ZBP1 directs local translation in microglial processes to regulate motility and phagocytosis during inflammation

Polarized cells in the brain, such as neurons and glia, rely on the asymmetric distribution of their proteins compartmentalizing the function of dendr... Read more...

TDP-43 dysregulation impairs cholesterol metabolism linked with myelination defects

TDP-43 is a nuclear protein encoded by the TARDBP gene, which forms pathological aggregates in various neurodegenerative diseases, collectively known ... Read more...

Corrigendum to “TDP-43-M323K causes abnormal brain development and progressive cognitive and motor deficits associated with mislocalised and increased levels of TDP-43” [Neurobiology of disease Volume 193, April 2024, 106437]

No abstract... Read more...

In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use

TDP-43 proteinopathies are a heterogeneous group of neurodegenerative disorders that share the presence of aberrant, misfolded and mislocalized deposi... Read more...

Author Correction: Genetic-based patient stratification in Alzheimer’s disease

No abstract... Read more...

Genetic-based patient stratification in Alzheimer’s disease

Alzheimer's disease (AD) shows a high pathological and symptomatological heterogeneity. To study this heterogeneity, we have developed a patient strat... Read more...

TDP-43-M323K causes abnormal brain development and progressive cognitive and motor deficits associated with mislocalised and increased levels of TDP-43

TDP-43 pathology is found in several neurodegenerative disorders, collectively referred to as "TDP-43 proteinopathies". Aggregates of TDP-43 are prese... Read more...

Leptin haploinsufficiency exerts sex-dependent partial protection in SOD1G93A mice by reducing inflammatory pathways in the adipose tissue

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by significant metabolic disruptions, including weight loss an... Read more...

Mutation in the FUS nuclear localisation signal domain causes neurodevelopmental and systemic metabolic alterations

Variants in the ubiquitously expressed DNA/RNA-binding protein FUS cause aggressive juvenile forms of amyotrophic lateral sclerosis (ALS). Most FUS mu... Read more...

A data-driven approach to complement the A/T/(N) classification system using CSF biomarkers

CONCLUSION: We propose this data-driven three-group classification as a meaningful and straightforward approach to evaluating the risk of conversion t... Read more...

Discovery of Mitophagy Inhibitors with Therapeutic Potential in Different Familial Amyotrophic Lateral Sclerosis Mutations

Mitophagy is the selective degradation of mitochondria by autophagy. It promotes the turnover of mitochondria and prevents the accumulation of dysfunc... Read more...

Lipid Metabolic Alterations in the ALS-FTD Spectrum of Disorders

There is an increasing interest in the study of the relation between alterations in systemic lipid metabolism and neurodegenerative disorders, in part... Read more...

Body Complexion and Circulating Lipids in the Risk of TDP-43 Related Disorders

CONCLUSION: This work provides evidence that body complexion and circulating lipids traits impact differentially on the risk of FTD and ALS, suggestin... Read more...

Erratum: Generation and analysis of innovative genomically humanized knockin SOD1, TARDBP (TDP-43), and FUS mouse models

[This corrects the article DOI: 10.1016/j.isci.2021.103463.].... Read more...

Generation and analysis of innovative genomically humanized knockin SOD1, TARDBP (TDP-43), and FUS mouse models

Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) is a fatal neurodegenerative disorder, and continued innovation is needed for improved... Read more...

A Transcriptomic Meta-Analysis Shows Lipid Metabolism Dysregulation as an Early Pathological Mechanism in the Spinal Cord of SOD1 Mice

Amyotrophic lateral sclerosis (ALS) is a multifactorial and complex fatal degenerative disorder. A number of pathological mechanisms that lead to moto... Read more...

The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour

Members of the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) protein family are associated with multiple neurodevelopmental disor... Read more...

Uses for humanised mouse models in precision medicine for neurodegenerative disease

Neurodegenerative disease encompasses a wide range of disorders afflicting the central and peripheral nervous systems and is a major unmet biomedical ... Read more...

Loss of Frrs1l disrupts synaptic AMPA receptor function, and results in neurodevelopmental, motor, cognitive and electrographical abnormalities

Loss-of-function mutations in a human AMPA receptor-associated protein, ferric chelate reductase 1-like (FRRS1L), are associated with a devastating ne... Read more...

Skeletal Muscle Modulates Huntington’s Disease Pathogenesis in Mice: Role of Physical Exercise

Huntington's disease (HD) is a monogenic fatal neurodegenerative disorder. However, there is increasing evidence that HD is a pleiotropic systemic dis... Read more...

Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis

TDP-43 (encoded by the gene TARDBP) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how TARDBP ... Read more...

ZNRF3 functions in mammalian sex determination by inhibiting canonical WNT signaling

Mammalian sex determination is controlled by the antagonistic interactions of two genetic pathways: The SRY-SOX9-FGF9 network promotes testis determin... Read more...

A genetic modifier suggests that endurance exercise exacerbates Huntington’s disease

Polyglutamine expansions in the huntingtin gene cause Huntington's disease (HD). Huntingtin is ubiquitously expressed, leading to pathological alterat... Read more...

Cartilage regeneration and ageing: Targeting cellular plasticity in osteoarthritis

Ageing processes play a major contributing role for the development of Osteoarthritis (OA). This prototypic degenerative condition of ageing is the mo... Read more...

Loss-of-Function Mutations in FRRS1L Lead to an Epileptic-Dyskinetic Encephalopathy

Glutamatergic neurotransmission governs excitatory signaling in the mammalian brain, and abnormalities of glutamate signaling have been shown to contr... Read more...

Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration

Zinc finger motifs are distributed amongst many eukaryotic protein families, directing nucleic acid-protein and protein-protein interactions. Zinc fin... Read more...

A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity

Transgenic mouse models expressing mutant superoxide dismutase 1 (SOD1) have been critical in furthering our understanding of amyotrophic lateral scle... Read more...

Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis

Mutations in the skeletal muscle channel (SCN4A), encoding the Nav1.4 voltage-gated sodium channel, are causative of a variety of muscle channelopathi... Read more...

Reducing Igf-1r levels leads to paradoxical and sexually dimorphic effects in HD mice

Many of the neurodegenerative diseases that afflict people in later life are associated with the formation of protein aggregates. These so-called "pro... Read more...

IGF-1 receptor antagonism inhibits autophagy

Inhibition of the insulin/insulin-like growth factor signalling pathway increases lifespan and protects against neurodegeneration in model organisms, ... Read more...

α-Synuclein levels affect autophagosome numbers in vivo and modulate Huntington disease pathology

Huntington and Parkinson diseases (HD and PD) are two major neurodegenerative disorders pathologically characterized by the accumulation of the aggreg... Read more...

α-Synuclein levels modulate Huntington’s disease in mice

α-Synuclein and mutant huntingtin are the major constituents of the intracellular aggregates that characterize the pathology of Parkinson's disease (P... Read more...

α-Synuclein impairs macroautophagy: implications for Parkinson’s disease

Parkinson's disease (PD) is characterized pathologically by intraneuronal inclusions called Lewy bodies, largely comprised of α-synuclein. Multiplicat... Read more...

Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington’s disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a polyglutamine expansion in huntingtin. There are no treatment... Read more...

Functional and structural modifications during retinal degeneration in the rd10 mouse

Mouse models of retinal degeneration are useful tools to study therapeutic approaches for patients affected by hereditary retinal dystrophies. We have... Read more...

Attenuation of vision loss and delay in apoptosis of photoreceptors induced by proinsulin in a mouse model of retinitis pigmentosa

CONCLUSIONS: These results provide a new basis for possible therapies to counteract retinitis pigmentosa and a new tool to characterize the mechanisms... Read more...

Proinsulin/insulin is synthesized locally and prevents caspase- and cathepsin-mediated cell death in the embryonic mouse retina

Programmed cell death is an essential, highly regulated process in neural development. Although the role of insulin-like growth factor I in supporting... Read more...