Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.8K
Amyloid Fibrils03:03

Amyloid Fibrils

9.8K
Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
9.8K
Fibronectins Connect Cells with ECM01:25

Fibronectins Connect Cells with ECM

2.5K
Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
2.5K
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

2.5K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.5K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Integration analysis of lncRNA and mRNA expression data identifies DOCK4 as a potential biomarker for elderly osteoporosis.

BMC medical genomics·2024
Same author

A systematic review and meta-analysis of the anti-tumor effects of Paeoniae Radix Rubra in animal models.

Journal of ethnopharmacology·2024
Same author

Resilience conferred by APOE-R136S: a defense bestowed by nature to combat Alzheimer's disease.

Signal transduction and targeted therapy·2024
Same author

Enhanced NMDA receptor pathway and glutamate transmission in the hippocampal dentate gyrus mediate the spatial learning and memory impairment of obese rats.

Pflugers Archiv : European journal of physiology·2024
Same author

Benzodiazepines and mortality: Consideration of potential confounders.

Pain practice : the official journal of World Institute of Pain·2024
Same author

Myxoma with rich blood supply in the left atrium.

Echocardiography (Mount Kisco, N.Y.)·2024

Related Experiment Video

Updated: Sep 8, 2025

Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
09:16

Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation

Published on: June 26, 2018

7.6K

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

Zifeng Huang1, Hui Zhong1, Yingqiong Lu2

  • 1Department of Neurology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510280, PR China.

Neurotherapeutics : the Journal of the American Society for Experimental Neurotherapeutics
|September 5, 2025
PubMed
Summary

Cellular fibronectin (cFn) exacerbates Parkinson's disease pathology by damaging mitochondria and disrupting lipid metabolism through integrin α4β1, leading to α-synuclein aggregation. Targeting cFn may offer a new therapeutic approach for PD.

Keywords:
FibronectinMitochondrial dysfunctionParkinson's diseasePoly (ADP‒ribose) (PAR) polymerase-1Stearoyl-CoA desaturaseα-Synuclein

More Related Videos

A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model
08:24

A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model

Published on: November 25, 2022

2.3K
Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons
10:03

Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons

Published on: August 16, 2020

10.7K

Related Experiment Videos

Last Updated: Sep 8, 2025

Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
09:16

Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation

Published on: June 26, 2018

7.6K
A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model
08:24

A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model

Published on: November 25, 2022

2.3K
Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons
10:03

Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons

Published on: August 16, 2020

10.7K

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Mitochondrial dysfunction and lipid dysregulation are implicated in Parkinson's disease (PD) pathogenesis.
  • The role of extracellular matrix components, such as cellular fibronectin (cFn), in PD-related pathological mechanisms is not well understood.

Purpose of the Study:

  • To investigate whether cellular fibronectin (cFn) contributes to α-synuclein (α-syn) abnormality in Parkinson's disease (PD).
  • To elucidate the mechanisms by which cFn may induce mitochondrial energy depletion and disrupt lipid homeostasis.

Main Methods:

  • Utilized 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated PD mouse models and human neuronal SH-SY5Y cells.
  • Employed astrocyte-derived cFn delivery and AAV-mediated cFn knockdown models.
  • Assessed mitochondrial dysfunction via transmission electron microscopy (TEM) and measured levels of poly (ADP-ribose) polymerase-1 (PARP1), α-syn, and cFn-induced lipid dysmetabolism.

Main Results:

  • Excessive cFn accumulation in the substantia nigra pars compacta (SNpc) of MPTP-treated mice correlated with exacerbated neuronal mitochondrial dysfunction and α-syn aggregation.
  • cFn activated PARP1 and induced NAD+ depletion via integrin α4β1, promoting α-syn aggregation.
  • cFn increased free fatty acids and triglycerides by binding to integrin α4β1, synergistically worsening α-syn abnormality.
  • cFn activated stearoyl-CoA desaturase (SCD) via integrin α4β1 interaction.
  • Genetic cFn depletion rescued mitochondrial and α-syn pathologies in MPTP-treated mice.

Conclusions:

  • Cellular fibronectin (cFn) exacerbates α-syn aggregation in Parkinson's disease through integrin α4β1-mediated activation of PARP1 and SCD.
  • These pathways lead to mitochondrial dysfunction and lipid dysmetabolism, contributing to PD progression.
  • Targeting cFn presents a potential therapeutic strategy for Parkinson's disease.