Cellular fibronectin exacerbates α-synuclein aggregation via integrin alpha4beta1 mediated PARP1 and SCD elevation.

Mitochondrial dysfunction and lipid metabolic disturbance may promote pathologic α-synuclein (α-syn) aggregation, accelerating the progression of Parkinson's disease (PD). Whether extracellular matrices are associated with those pathological mechanisms in PD remains elusive. Here, we aimed to identify if cellular fibronectin (cFn), a component of extracellular matrices, contributes to α-syn abnormality via inducing mitochondrial energy depletion or disrupting lipid homeostasis.

Fibrinogen exacerbates α-synuclein aggregation and mitochondrial dysfunction via alpha5beta3 integrin in Parkinson's disease.

Introduction: Blood-brain barrier(BBB) disruption promotes the influx of the fibrinogen(FG); however, it remains unknown whether FG deposit contributes to neurodegeneration in Parkinson's disease(PD).

Objectives: We aimed to examine the pathophysiologic link among FG, mitochondrial dysfunction and α-synuclein(α-syn) abnormality in PD.

Methods: First, plasma FG levels were measured in 60 healthy controls and 60 PD patients.

Fibrinogen degradation products exacerbate alpha-synuclein aggregation by inhibiting autophagy via downregulation of Beclin1 in multiple system atrophy.

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease arising from accumulation of the α-synuclein and aberrant protein clearance in oligodendrocytes. The mechanisms of autophagy involved in the progression of MSA remain poorly understood. It is reported that MSA patients have blood-brain barrier impairments, which may increase the entry of fibrinogen into the brain.

Tuning the structure and function of metal-organic frameworks via linker design.

Metal-organic frameworks (MOFs) are constructed from metal ions/clusters coordinated by organic linkers (or bridging-ligands). The hallmark of MOFs is their permanent porosity, which is frequently found in MOFs constructed from metal-clusters. These clusters are often formed in situ, whereas the linkers are generally pre-formed.

Symmetry-guided synthesis of highly porous metal-organic frameworks with fluorite topology.

Two stable, non-interpenetrated MOFs, PCN-521 and PCN-523, were synthesized by a symmetry-guided strategy. Augmentation of the 4-connected nodes in the fluorite structure with a rigid tetrahedral ligand and substitution of the 8-connected nodes by the Zr/Hf clusters yielded MOFs with large octahedral interstitial cavities. They are the first examples of Zr/Hf MOFs with tetrahedral linkers.