Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Neural Regulation

Neural Regulation

Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.

Amyloid Fibrils

Amyloid Fibrils

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,...

Regulation of Nuclear Protein Sorting

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...

You might also read

Related Articles

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

Sort by

Same authorSame journal

PERK deficiency amplifies molecular, structural, and network vulnerability to repetitive mild traumatic brain injury.

Neurobiology of disease·2026

Same author

Robust tauopathy and memory deficits in a mouse model constitutively overexpressing human P301L MAPT.

Neurobiology of disease·2026

Same author

The Biological Fate of DBS Leads After 15 Years of Stimulation.

Movement disorders clinical practice·2026

Same author

Drivers of Research Participation Among Racially and Ethnically Underrepresented Women: Insights from Semi-Structured Interviews.

Journal of racial and ethnic health disparities·2026

Same author

Length of gestation and postpartum visit attendance.

Pregnancy (Hoboken, N.J.)·2026

Same author

Hyperglycosylation is a metabolic driver of Alzheimer's disease.

Nature metabolism·2026

Search research articles

Related Experiment Video

Updated: Sep 15, 2025

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

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

Published on: August 16, 2020

Pathological α-synuclein perturbs nuclear integrity.

Michael Millett¹, Allison Comite¹, Elisabeth Martin Castosa¹

¹Department of Pharmacology & Therapeutics and Center for Translational Research in Neurodegeneration, University of Florida College of Medicine, Gainesville, FL 32610, United States of America.

Neurobiology of Disease

|July 16, 2025

Summary

Pathological alpha-synuclein (α-synuclein) aggregates in the nucleus of brain cells, observed in synucleinopathies like Lewy Body Dementia, disrupt nuclear function and integrity, leading to DNA damage and increased toxin sensitivity.

Keywords:

Laminopathy Lewy body dementia Nuclear dysfunction Α-synuclein

More Related Videos

Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains

Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains

Published on: January 5, 2016

Technique for Intranasal Administration of α-Synuclein Aggregates

Technique for Intranasal Administration of α-Synuclein Aggregates

Published on: November 8, 2024

Related Experiment Videos

Last Updated: Sep 15, 2025

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

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

Published on: August 16, 2020

Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains

Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains

Published on: January 5, 2016

Technique for Intranasal Administration of α-Synuclein Aggregates

Technique for Intranasal Administration of α-Synuclein Aggregates

Published on: November 8, 2024

Area of Science:

Neuroscience
Molecular Biology
Cell Biology

Background:

Synucleinopathies, including Lewy Body Dementia, are characterized by pathological alpha-synuclein aggregates.
The precise role of alpha-synuclein in nuclear function remains controversial and poorly understood.
Emerging evidence suggests alpha-synuclein plays a role in synaptic regulation, but its nuclear presence and impact are unclear.

Purpose of the Study:

To investigate the nuclear localization of pathological alpha-synuclein in synucleinopathy models and human tissue.
To determine the downstream consequences of nuclear alpha-synuclein accumulation on nuclear integrity and function.
To elucidate the role of nuclear alpha-synuclein in disease pathogenesis.

Main Methods:

Utilized synucleinopathy murine and cell culture models, alongside postmortem Lewy Body Dementia human brain tissue.
Employed quantitative super-resolution microscopy to visualize alpha-synuclein localization within nuclear compartments.
Assessed nuclear morphology, DNA damage markers (53BP1), nuclear envelope integrity, RNA localization, and sensitivity to nuclear toxins.

Main Results:

Pathological alpha-synuclein aggregates were observed within the nucleus in both mouse models and human Lewy Body Dementia cortex.
Nuclear alpha-synuclein accumulation correlated with abnormal nuclear morphology in affected tissues.
Elevated DNA damage markers, nuclear envelope damage, and altered RNA localization were observed in synucleinopathy models with nuclear alpha-synuclein.

Conclusions:

This study rigorously demonstrates nuclear localization of pathological alpha-synuclein using advanced microscopy.
Nuclear accumulation of pathological alpha-synuclein disrupts nuclear integrity and function, contributing to disease pathology.
Findings provide novel insights into the detrimental impact of nuclear alpha-synuclein in synucleinopathies.