A new clue to the cause of ALS and frontotemporal dementia

Good news! Hopefully, a breakthrough!

"... reactive nitrogen molecules in the human brain. These reactive molecules, which naturally increase in the brain with aging, can set off a damaging process in which an important protein, known as TDP-43, clumps together and loses its function in affected brain cells. ..."

"... in the absence of mutation (i.e., in the vast majority of “sporadic” cases), mechanisms for protein misfolding/aggregation remain largely unknown. Here, we show environmentally induced nitrosative stress triggers protein aggregation and cell-to-cell spread. In patient brains with amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD), aggregation of the RNA-binding protein TDP-43 constitutes a major component of aberrant cytoplasmic inclusions. We identify a pathological signaling cascade whereby reactive nitrogen species cause S-nitrosylation of TDP-43 (forming SNO-TDP-43) to facilitate disulfide linkage and consequent TDP-43 aggregation. Similar pathological SNO-TDP-43 levels occur in postmortem human FTD/ALS brains and in cell-based models, including human-induced pluripotent stem cell (hiPSC)-derived neurons. ..."

A new clue to the cause of ALS and frontotemporal dementia | Scripps Research Scientists find evidence that reactive nitrogen molecules, abundant in old age, can trigger the disease process for two highly fatal conditions.

Here is the link to the underlying research paper:

S-nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD

Mitochondria that self-destruct in a weird way may play a role in ALS

Amazing stuff! 

"mitoautophagy.” It is a distinct process from mitophagy, the usual way that cellular structures called autophagosomes and lysosomes remove damaged mitochondria from the cell ...  mitochondria appear to dismantle themselves without help from usual cell demolition [process]"


Mitochondria that self-destruct in a weird way may play a role in ALS | Science News: Mitochondria that appear to dismantle themselves in certain brain cells may be a first step toward ALS, a mouse study suggests. In upper motor nerve cells in mice, the cell organelles formed loops that then disintegrated