Discovery Of A New ALS And Dementia Disease Mechanism Raises Treatment Hopes

[aussiegirl]

https://vervetimes.com/discovery-of-a-new-als-and-dementia-disease-mechanism-raises-treatment-hopes-sciencedaily/

[LindaB]

Thanks aussiegirl xx

[Johnny5]

This is the actual study. Cannot access the whole study without subscription.

• Article
• Published: 08 December 2021

Structure of pathological TDP-43 filaments from ALS with FTLD

Nature volume 601, pages139–143 (2022)

Abstract


The abnormal aggregation of TAR DNA-binding protein 43 kDa (TDP-43) in neurons and glia is the defining pathological hallmark of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and multiple forms of frontotemporal lobar degeneration (FTLD)^1,2. It is also common in other diseases, including Alzheimer’s and Parkinson’s. No disease-modifying therapies exist for these conditions and early diagnosis is not possible. The structures of pathological TDP-43 aggregates are unknown. Here we used cryo-electron microscopy to determine the structures of aggregated TDP-43 in the frontal and motor cortices of an individual who had ALS with FTLD and from the frontal cortex of a second individual with the same diagnosis. An identical amyloid-like filament structure comprising a single protofilament was found in both brain regions and individuals. The ordered filament core spans residues 282–360 in the TDP-43 low-complexity domain and adopts a previously undescribed double-spiral-shaped fold, which shows no similarity to those of TDP-43 filaments formed in vitro^3,4. An abundance of glycine and neutral polar residues facilitates numerous turns and restricts β-strand length, which results in an absence of β-sheet stacking that is associated with cross-β amyloid structure. An uneven distribution of residues gives rise to structurally and chemically distinct surfaces that face external densities and suggest possible ligand-binding sites. This work enhances our understanding of the molecular pathogenesis of ALS and FTLD and informs the development of diagnostic and therapeutic agents that target aggregated TDP-43.

[matthew55]

Brains, brains. 😂😁😉🤣xx

[denise]

Like I can understand this. Anyone able to translate 😳

[Ellie]

This is the actual study. Cannot access the whole study without subscription.

That is a different paper to the one about which the OP posted.

For anyone wanting to read the full scientific paper relating to this thread's topic, published in Nature on 23/02/2022, click here to be bamboozled.

It is heavy reading but thankfully the MNDA's research blog sums up the paper for us in a much more reader-friendly way, available here

[matthew55]

Traditional zombie chant 👿😁😄🤩xx