C9orf72-mediated ALS and FTD: multiple pathways to disease

R Balendra, AM Isaacs - Nature Reviews Neurology, 2018 - nature.com
The discovery that repeat expansions in the C9orf72 gene are a frequent cause of
amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) has revolutionized …

CRISPR-based functional genomics for neurological disease

M Kampmann - Nature Reviews Neurology, 2020 - nature.com
Neurodegenerative, neurodevelopmental and neuropsychiatric disorders are among the
greatest public health challenges, as many lack disease-modifying treatments. A major …

[HTML][HTML] Trans effects on gene expression can drive omnigenic inheritance

X Liu, YI Li, JK Pritchard - Cell, 2019 - cell.com
Early genome-wide association studies (GWASs) led to the surprising discovery that, for
typical complex traits, most of the heritability is due to huge numbers of common variants …

[HTML][HTML] p53 is a central regulator driving neurodegeneration caused by C9orf72 poly (PR)

M Maor-Nof, Z Shipony, R Lopez-Gonzalez… - Cell, 2021 - cell.com
The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal
dementia (FTD) is a GGGGCC repeat expansion in the C9orf72 gene. We developed a …

PIKFYVE inhibition mitigates disease in models of diverse forms of ALS

ST Hung, GR Linares, WH Chang, Y Eoh, G Krishnan… - Cell, 2023 - cell.com
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results from
many diverse genetic causes. Although therapeutics specifically targeting known causal …

Heterochromatin anomalies and double-stranded RNA accumulation underlie C9orf72 poly(PR) toxicity

YJ Zhang, L Guo, PK Gonzales, TF Gendron, Y Wu… - Science, 2019 - science.org
INTRODUCTION Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS)
are fatal neurodegenerative diseases that share clinical and neuropathological features …

Regulators of mitonuclear balance link mitochondrial metabolism to mtDNA expression

NJ Kramer, G Prakash, RS Isaac, K Choquet, I Soto… - Nature Cell …, 2023 - nature.com
Mitochondrial oxidative phosphorylation (OXPHOS) complexes are assembled from proteins
encoded by both nuclear and mitochondrial DNA. These dual-origin enzymes pose a …

[HTML][HTML] C9ORF72 GGGGCC repeat-associated non-AUG translation is upregulated by stress through eIF2α phosphorylation

W Cheng, S Wang, AA Mestre, C Fu, A Makarem… - Nature …, 2018 - nature.com
Hexanucleotide repeat expansion in C9ORF72 is the most frequent cause of both
amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we …

[HTML][HTML] Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq

JM Replogle, RA Saunders, AN Pogson, JA Hussmann… - Cell, 2022 - cell.com
A central goal of genetics is to define the relationships between genotypes and phenotypes.
High-content phenotypic screens such as Perturb-seq (CRISPR-based screens with single …

[HTML][HTML] Advances of zebrafish in neurodegenerative disease: from models to drug discovery

X Wang, JB Zhang, KJ He, F Wang… - Frontiers in Pharmacology, 2021 - frontiersin.org
Neurodegenerative disease (NDD), including Alzheimer's disease, Parkinson's disease, and
amyotrophic lateral sclerosis, are characterized by the progressive loss of neurons which …