MRI susceptibility map weighted imaging (SMWI) as a neurodegeneration biomarker in the prodromal to overt alpha-synucleinopathy continuum.
Authors: Falcitano L, Calizzano F, Mattioli P, Kiersnowski OC, Avanzino L, Girtler NG, Diociasi A, Losa M, Massa F, Morbelli S, Orso B, Pelosin E, Bonassi G, Raffa S, Pardini M, Costagli M, Roccatagliata L, Arnaldi D
Journal: Journal of Parkinson's disease
mental health
psychology
open access
Abstract
Endogenous and exogenous peptides can undergo conformational changes
and self-associate to form deposits in various organs. These peptide
aggregates are resistant to enzymatic degradation in both extracellular
and intracellular compartments. Endogenous peptide or protein aggregates
are linked to more than 50 human diseases, including neurodegenerative
disorders like prion disease, Alzheimer’s disease (AD), and
Parkinson’s disease (PD), as well as metabolic syndromes like
type II diabetes and other metabolic storage diseases such as Cardiac
amyloidosis. The formation of such deposits composed of amyloid fibrils is preceded
by the emergence of soluble, metastable, and transient intermediates,
referred to as oligomers, and fibril-type core structures known as
protofibrils. The amyloid fibrils observed in
different pathologies share structural similarities in their quaternary
structure and ultrastructure, characterized by a cross-β backbone. Since various aggregation species share the same process, identifying
the specific nanostructure responsible for observed toxicity is often
challenging. As a result, many molecular mechanisms and interactions
involved in amyloid protein/peptide misfolding and aggregation remain
poorly understood, limiting therapeutic intervention. Furthermore, the environmental triggers or cofactors that contribute
to amyloid aggregation and subsequent disease development remain elusive.
Representative peptides involved in amyloid-related diseases include
the amyloid-β (Aβ) peptides derived from the amyloid β
precursor protein (APP), which are considered the culprits in AD (A). Schematic representations of the self-assembling processes of the
endogenous Amyloid-β and one of the most relevant peptides in
gluten-related disorders, the 33-mer gliadin peptide (33-mer). Created
with . Interestingly, while Aβ research has primarily focused
on
the brain, studies in animal modelsnot fully detailed heresuggest that peripheral Aβ oligomerization in the gut
may be crucial in the early stages of AD. The gut-brain axis refers to the bidirectional communication network
between the gastrointestinal tract, including its resident microbiota,
and the central nervous system (CNS). This interaction is mediated through neural pathways, including
the vagus nerve, as well as through the sympathetic and parasympathetic
branches of the autonomic nervous system and proprioceptive fibers.
This complex circuit exchanges various signaling molecules, such as
neurotransmitters (e.g., serotonin and GABA), neuropeptides, cytokines,
and microbial metabolites such as short-chain fatty acids (SCFAs).
These signaling molecules influence the gastrointestinal physiology
and immune responses, affecting brain function and disease development.
and self-associate to form deposits in various organs. These peptide
aggregates are resistant to enzymatic degradation in both extracellular
and intracellular compartments. Endogenous peptide or protein aggregates
are linked to more than 50 human diseases, including neurodegenerative
disorders like prion disease, Alzheimer’s disease (AD), and
Parkinson’s disease (PD), as well as metabolic syndromes like
type II diabetes and other metabolic storage diseases such as Cardiac
amyloidosis. The formation of such deposits composed of amyloid fibrils is preceded
by the emergence of soluble, metastable, and transient intermediates,
referred to as oligomers, and fibril-type core structures known as
protofibrils. The amyloid fibrils observed in
different pathologies share structural similarities in their quaternary
structure and ultrastructure, characterized by a cross-β backbone. Since various aggregation species share the same process, identifying
the specific nanostructure responsible for observed toxicity is often
challenging. As a result, many molecular mechanisms and interactions
involved in amyloid protein/peptide misfolding and aggregation remain
poorly understood, limiting therapeutic intervention. Furthermore, the environmental triggers or cofactors that contribute
to amyloid aggregation and subsequent disease development remain elusive.
Representative peptides involved in amyloid-related diseases include
the amyloid-β (Aβ) peptides derived from the amyloid β
precursor protein (APP), which are considered the culprits in AD (A). Schematic representations of the self-assembling processes of the
endogenous Amyloid-β and one of the most relevant peptides in
gluten-related disorders, the 33-mer gliadin peptide (33-mer). Created
with . Interestingly, while Aβ research has primarily focused
on
the brain, studies in animal modelsnot fully detailed heresuggest that peripheral Aβ oligomerization in the gut
may be crucial in the early stages of AD. The gut-brain axis refers to the bidirectional communication network
between the gastrointestinal tract, including its resident microbiota,
and the central nervous system (CNS). This interaction is mediated through neural pathways, including
the vagus nerve, as well as through the sympathetic and parasympathetic
branches of the autonomic nervous system and proprioceptive fibers.
This complex circuit exchanges various signaling molecules, such as
neurotransmitters (e.g., serotonin and GABA), neuropeptides, cytokines,
and microbial metabolites such as short-chain fatty acids (SCFAs).
These signaling molecules influence the gastrointestinal physiology
and immune responses, affecting brain function and disease development.