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\begin{document}

\title{Discovered in plants a mechanism that corrects defects in proteins such
as those that cause Alzheimer's and Parkinson's Diseases in humans}



\author[1]{Ernesto Llamas }%
\author[2]{Pablo Pulido}%
\author[2]{Zoila Babot}%
\author[2]{Manuel Rodriguez-Concepcion}%
\affil[1]{Journal of Sketching Science}%
\affil[2]{Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB, Campus UAB Bellaterra, Barcelona, Spain}%


\vspace{-1em}



  
  \date{May 17, 2024}


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Various age-related neurodegenerative diseases, such as amyotrophic
lateral sclerosis (ALS), Alzheimer's, Huntington's, and Parkinson's, are
associated with the same basic disorder: the loss of nerve cells
capacity to fold their proteins correctly, which causes~\textbf{protein
aggregations} that form ``clumps'' that end up generating the cell death
(Figure 1). To better understand~\textbf{protein folding} let's
visualize folded proteins as a folded paper plane when both have a
correct 3D conformation they can accomplish their respective functions,
catalyze a reaction, in the case of some proteins or fly in the case of
the plane. Incorrect folding cause that proteins lose their normal
functions and cause protein aggregations that form ``clumps'' that end
up generating the cell death. Analogously, a paper plane incorrectly
folded would not be able to fly and would form a paper ball with other
defective paper planes. With this example is easier to understand the
conformation or shapes that some proteins acquire (Figure 1).~

\par\null\selectlanguage{english}
\begin{figure}[h!]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/01-Figure-Proteins-papers/01-Figure-Proteins-papers}
\caption{{Some age-related diseases are caused by protein aggregation in nerve
cells (blue panel). Schematic representation of protein conformations
and visualized as paper planes (yellow and red panels).~
{\label{188062}}%
}}
\end{center}
\end{figure}

~Plants, like animals, use proteins to carry out the cellular functions
that keep them alive. The protein composition is determined by the
information present in the cellular DNA, but to exercise their
biological function, the proteins must also be folded in a 3D
configuration, like the correctly folded paper plane. However, in stress
situations, such as a sudden increase in temperature, cause missteps in
the folding process, thus producing misfolded proteins that have to be
either removed or repaired. Otherwise they could cluster and form toxic
aggregates.

~Chloroplasts are the cellular compartments where the photosynthesis
takes place in plant cells. Also, they are responsible for producing
many of the nutrients that allow the growth of plants and of animals
that ingest them. A big part of this work is carried out by proteins,
some of which are very prone to misfold and aggregate, thus losing their
function.

Under normal conditions, chloroplasts get rid of these defective
proteins by degrading them using the molecular machinery called protease
Clp. However, when the accumulation of aggregated proteins exceeds the
ability of the Clp protease to remove them, the chloroplasts generate
a~\textbf{distress signal}~that travels to the nucleus of the cell
to~\textbf{activate the production of repair proteins, called
chaperones}. The chaperones, in turn, are transported to the
chloroplasts to undo the protein ``lumps'' and unfold the disaggregated
proteins, favoring that they can be folded back correctly and recover
their function in a few hours. Based on Figure 1 we can assume that
hands correcting the folding defects of our paper plane are the
chaperones. These molecular mechanisms are similar to those that work in
our nerve cells when misfolded proteins are produced in the
mitochondria. In Figure 2 we illustrate this communication between
chloroplast and nucleus, in which chloroplast with aggregated proteins
send a WhatsApp message to the nucleus, and ask for help. The nucleus
receives the message and sends chaperones to eliminate protein
aggregation.~

\par\null\selectlanguage{english}
\begin{figure}[h!]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/02-Figure-Plants/02-Figure-Plants}
\caption{{Plants use proteins to carry out cellular functions like photosynthesis
in chloroplasts (blue panel). In stress situations, such as a sudden
increase in temperature, cause protein aggregation and hence chloroplast
malfunction.~~Chloroplast somehow senses the accumulation of aggregated
proteins and generates a~distress signal (Whatsapp message) that travels
into the nucleus of the cell to~activate the production of repair
proteins, called chaperones. Chaperones disaggregate and unfold the
proteins, favoring that they can be folded back correctly and recover
their function.
{\label{758232}}%
}}
\end{center}
\end{figure}

Our work was conducted using the model plant~\emph{Arabidopsis
thaliana}~and published in the journal~\textbf{PLOS
Genetics~\cite{28937985}}. We discovered that the key gene
-\emph{HsfA2}- activates the chaperone synthesis and thus rescues the
cell from the toxic effects produced by misfolded protein accumulations.
This key gene is also activated when a heat stroke causes problems of
protein folding in other cellular compartments. Knowing how plants
respond to the challenge of having some of their proteins lose their
original structure and function, becoming potentially dangerous, is
essential for better crop adaptation to adverse environmental
conditions. This challenge is particularly relevant in the current
context of climate change.

This research, conducted at \href{https://www.cragenomica.es/}{Centre
for Research in Agricultural Genomics (CRAG)}, may also help to better
understand how protein-misfolding in nervous system diseases start,
spread, and aggravate. The result of this research with plants could be
transferred to new universal methods to correct the protein misfolding
and thus impact the search for solutions to degenerative diseases that,
to this day, remain incurable.

\par\null

\section*{Contributions}

{\label{797602}}

Ernesto Llamas, Pablo Pulido, and Manuel Rodriguez-Concepcion wrote the
article. Zoila Babot, edited the article. Ernesto Llamas
(\href{https://www.instagram.com/eellamas}{@eellamas}) made the
illustrations.~

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