Aging in a dish: iPSC-derived and directly induced neurons for studying brain aging and age-related neurodegenerative diseases

J Mertens, D Reid, S Lau, Y Kim… - Annual review of …, 2018 - annualreviews.org
Age-associated neurological diseases represent a profound challenge in biomedical
research as we are still struggling to understand the interface between the aging process …

Mitochondrial aspects of synaptic dysfunction in Alzheimer's disease

Q Cai, P Tammineni - Journal of Alzheimer's disease, 2017 - content.iospress.com
Alzheimer's disease (AD) is characterized by brain deposition of amyloid plaques and tau
neurofibrillary tangles along with steady cognitive decline. Synaptic damage, an early …

Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer's patients

J Mertens, JR Herdy, L Traxler, ST Schafer… - Cell stem cell, 2021 - cell.com
Sporadic Alzheimer's disease (AD) exclusively affects elderly people. Using direct
conversion of AD patient fibroblasts into induced neurons (iNs), we generated an age …

Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects

J Mertens, ACM Paquola, M Ku, E Hatch, L Böhnke… - Cell stem cell, 2015 - cell.com
Aging is a major risk factor for many human diseases, and in vitro generation of human
neurons is an attractive approach for modeling aging-related brain disorders. However …

Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS

A Jovičić, J Mertens, S Boeynaems, E Bogaert… - Nature …, 2015 - nature.com
C9orf72 mutations are the most common cause of amyotrophic lateral sclerosis (ALS) and
frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs) produced by …

Developmental regulation of tau splicing is disrupted in stem cell-derived neurons from frontotemporal dementia patients with the 10+ 16 splice-site mutation in MAPT

T Sposito, E Preza, CJ Mahoney… - Human molecular …, 2015 - academic.oup.com
The alternative splicing of the tau gene, MAPT, generates six protein isoforms in the adult
human central nervous system (CNS). Tau splicing is developmentally regulated and …

Tau isoforms imbalance impairs the axonal transport of the amyloid precursor protein in human neurons

V Lacovich, SL Espindola, M Alloatti… - Journal of …, 2017 - Soc Neuroscience
Tau, as a microtubule (MT)-associated protein, participates in key neuronal functions such
as the regulation of MT dynamics, axonal transport, and neurite outgrowth. Alternative …

Tau physiology and pathomechanisms in frontotemporal lobar degeneration

LG Bodea, A Eckert, LM Ittner, O Piguet… - Journal of …, 2016 - Wiley Online Library
Frontotemporal lobar degeneration (FTLD) has been associated with toxic intracellular
aggregates of hyperphosphorylated tau (FTLD‐tau). Moreover, genetic studies identified …

Next‐generation disease modeling with direct conversion: a new path to old neurons

L Traxler, F Edenhofer, J Mertens - FEBS letters, 2019 - Wiley Online Library
Within just over a decade, human reprogramming‐based disease modeling has developed
from a rather outlandish idea into an essential part of disease research. While iPSCs are a …

Druggable transcriptomic pathways revealed in Parkinson's patient-derived midbrain neurons

M van den Hurk, S Lau, MC Marchetto… - npj Parkinson's …, 2022 - nature.com
Complex genetic predispositions accelerate the chronic degeneration of midbrain substantia
nigra neurons in Parkinson's disease (PD). Deciphering the human molecular makeup of PD …