Interaction of amyloidogenic proteins in pancreatic β cells from subjects with synucleinopathies

  title={Interaction of amyloidogenic proteins in pancreatic $\beta$ cells from subjects with synucleinopathies},
  author={Ivan Mart{\'i}nez-Valbuena and Irene Amat-Villegas and Rafael Valenti-Azcarate and Mar Carmona-Abell{\'a}n and Irene Marcilla and Mar{\'i}a Teresa Tu{\~n}{\'o}n and M. R. Luquin},
  journal={Acta Neuropathologica},
Parkinson’s disease patients experience a wide range of non-motor symptoms that may be provoked by deposits of phosphorylated α-synuclein in the peripheral nervous system. Pre-existing diabetes mellitus might be a risk factor for developing Parkinson’s disease, and indeed, nearly 60% of Parkinson’s disease patients are insulin resistant. Thus, we have investigated whether phosphorylated α-synuclein is deposited in pancreatic tissue of subjects with synucleinopathies. We studied pancreatic… 
Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein
This study shows, for the first time, that along with amylin, pancreatic α-synuclein, Aβ, PrP and tau may contribute together to the complex pathophysiology of type two diabetes and in the appearance of insulin resistance in Alzheimer's and Parkinson’s disease.
Amylin as a Potential Link between Type 2 Diabetes and Alzheimer Disease
The presence of both tau and Aβ inclusions in pancreatic β cells, and of amylin deposits in the brain, provides new evidence of a potential overlap in the mechanisms underlying the pathogenesis of T2DM and AD.
Cynomolgus Monkeys With Spontaneous Type-2-Diabetes-Mellitus-Like Pathology Develop Alpha-Synuclein Alterations Reminiscent of Prodromal Parkinson’s Disease and Related Diseases
The data indicates the close association between IAPP and α-synuclein and the potential link between T2 DM and PD, which implies that T2DM may facilitate PD disease onset and progress by interfering with the pathological protein aggregation both in the pancreatic islets and the brain.
Long-term hyperglycemia aggravates α-synuclein aggregation and dopaminergic neuronal loss in a Parkinson’s disease mouse model
The results solidify the potential link between DM and PD, providing insights into how hyperglycemia induces nigrostriatal degeneration and contributes to pathogenic mechanisms in PD.
Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus
  • B. Melnik
  • Biology, Medicine
    International journal of molecular sciences
  • 2021
Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial
α-Synuclein Regulates Peripheral Insulin Secretion and Glucose Transport
Data suggests that α-syn modulates both pancreatic beta cell function and glucose transport in peripheral tissues, thereby playing a pivitol role in the maintenance of normal glucose homeostasis.
Targeting hIAPP fibrillation: A new paradigm to prevent β-cell death?
This review gives a clear understanding of prion proteins, their structure, propagation and disease causing abilities and analyzed that diabetes mellitus could not be just a disease which is caused by insulin deficiency or resistance but could also be the consequence of protein misfolding.
Living with the enemy: from protein-misfolding pathologies we know, to those we want to know
Amyloid Cross-Seeding: Mechanism, Implication, and Inhibition
The amyloid proteins and the cross-seeding phenomena are discussed in detail and data suggest that targeting the common epitope of the interacting amyloids proteins may be a better therapeutic option than targeting only one species.


α-Synuclein is phosphorylated in synucleinopathy lesions
It is shown by mass spectrometry analysis and studies with an antibody that specifically recognizes phospho-Ser 129 of α-synuclein, that this residue is selectively and extensively phosphorylated in synucleinopathy lesions and promoted fibril formation in vitro.
Cross-talk between amyloidogenic proteins in type-2 diabetes and Parkinson’s disease
It is demonstrated that the two proteins cross-react and, importantly, the T2D amyloid protein can accelerate aS aggregation, which provides a possible explanation for why patients with type-2 diabetes are more prone to getting Parkinson’s disease.
α‐Synuclein oligomers and clinical implications for Parkinson disease
The possible role of α‐synuclein oligomers in cell death in Parkinson disease is reviewed and the potential clinical implications are discussed, as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders.
Multi-organ distribution of phosphorylated α-synuclein histopathology in subjects with Lewy body disorders
Spinal cord and peripheral PASH was most common in subjects with PD and DLB, where it appears likely that it is universally widespread, and within the gastrointestinal tract, there was a rostrocaudal gradient of decreasing PASH frequency and density.
Transactive DNA Binding Protein 43 Rather Than Other Misfolded Proteins in the Brain is Associated with Islet Amyloid Polypeptide in Pancreas in Aged Subjects with Diabetes Mellitus
There is no evidence of a link between AD-related pathology and DM in humans, whereas an association was found between pTDP43 and IAPP in DM, while the extent of misfolded proteins in the brain was higher in non-diabetes when compared with diabetics in demented.
α-Synuclein in Lewy bodies
Strong staining of Lewy bodies from idiopathic Parkinson's disease with antibodies for α-synuclein, a presynaptic protein of unknown function which is mutated in some familial cases of the disease, indicates that the LewY bodies from these two diseases may have identical compositions.
Distinct pattern of enteric phospho-alpha-synuclein aggregates and gene expression profiles in patients with Parkinson’s disease
The hypothesis that the CNS pathology of increased p-α-syn in PD also applies to the enteric nervous system of PD patients is strengthened, if elaborated morphometry is applied and give further insights in altered intestinal gene expression in PD.
Molecular interaction between type 2 diabetes and Alzheimer’s disease through cross-seeding of protein misfolding
It is observed that addition of IAPP seeds accelerates Aβ aggregation in vitro in a seeding-like manner and the resulting fibrils are composed of both peptides, suggesting that these peptides may directly interact and aggravate the disease.
Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism
It is shown that pancreatic IAPP aggregates can promote the misfolding and aggregation of endogenous IAPP in islet cultures obtained from transgenic mouse or healthy human pancreas, and this suggests that some of the pathologic and clinical alterations of T2D might be transmissible through a similar mechanism by which prions propagate in prion diseases.
The Search for a Peripheral Biopsy Indicator of &agr;-Synuclein Pathology for Parkinson Disease
The major finding reported herein was that biopsies can be used to distinguish PD patients from normal subjects, however, full assessment of the clinical potential of biopsy will only be achieved through large, multicenter trials in which both the initial detection methodology and histology have been assessed by blinded panels of pathologists.