Proteins Overview

Proteins Overview

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Proteins Overview</th>
</tr>
<tr>
<td class="label">Category</td>
<td>Key Proteins</td>
</tr>
<tr>
<td class="label">Aggregation</td>
<td>APP, Tau, α-syn, TDP-43</td>
</tr>
<tr>
<td class="label">Synaptic</td>
<td>Synaptophysin, PSD-95, NMDA-R</td>
</tr>
<tr>
<td class="label">Inflammatory</td>
<td>[TREM2](/proteins/trem2), CD33, IL-1β</td>
</tr>
<tr>
<td class="label">Transport</td>
<td>Dynein, Kinesin</td>
</tr>
<tr>
<td class="label">Transcription</td>
<td>TDP-43, FUS</td>
</tr>
<tr>
<td class="label">Chaperones</td>
<td>Hsp70, Hsp90</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer-disease" style="color:#ef9a9a">ALZHEIMER DISEASE</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1715 edges</a></td>
</tr>
</table>

Proteins Overview is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

Proteins Overview

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Proteins Overview</th>
</tr>
<tr>
<td class="label">Category</td>
<td>Key Proteins</td>
</tr>
<tr>
<td class="label">Aggregation</td>
<td>APP, Tau, α-syn, TDP-43</td>
</tr>
<tr>
<td class="label">Synaptic</td>
<td>Synaptophysin, PSD-95, NMDA-R</td>
</tr>
<tr>
<td class="label">Inflammatory</td>
<td>[TREM2](/proteins/trem2), CD33, IL-1β</td>
</tr>
<tr>
<td class="label">Transport</td>
<td>Dynein, Kinesin</td>
</tr>
<tr>
<td class="label">Transcription</td>
<td>TDP-43, FUS</td>
</tr>
<tr>
<td class="label">Chaperones</td>
<td>Hsp70, Hsp90</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer-disease" style="color:#ef9a9a">ALZHEIMER DISEASE</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1715 edges</a></td>
</tr>
</table>

Proteins Overview is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

This section covers proteins relevant to neurodegenerative diseases, including disease-associated proteins, therapeutic targets, and biomarkers. Understanding protein function, aggregation mechanisms, and therapeutic targeting is fundamental to developing disease-modifying treatments.

Major Protein Categories

Amyloid and APP Family

• [Amyloid Precursor Protein (APP](/proteins/amyloid-precursor-protein) — transmembrane protein cleaved by secretases to produce amyloid-beta. [APP](/entities/app-protein) mutations cause early-onset Alzheimer's disease.
• [Amyloid-beta (Aβ) peptides](/proteins/amyloid-beta) — main component of amyloid plaques in AD. Aβ42 is more aggregation-prone than Aβ40.
• [Amyloid-beta 42](/proteins/amyloid-beta-42) — Aβ isoform with higher tendency to form oligomers and plaques.

Tau Protein Family

• [Tau (MAPT) ](/proteins/tau) — microtubule-associated protein that forms neurofibrillary tangles. Six tau isoforms exist in human brain.
• [Phosphorylated tau](/proteins/phosphorylated-tau) — tau species with altered function in disease. Over 80 potential phosphorylation sites.

Synuclein Family

• [Alpha-synuclein](/proteins/alpha-synuclein) — Lewy body component in Parkinson's disease. 140 amino acid protein with N-terminal lipid-binding domain.
• [Beta-synuclein](/proteins/beta-synuclein) — synuclein family member with protective properties against aggregation.
• [Gamma-synuclein](/proteins/gamma-synuclein) — expressed in peripheral nervous system, implicated in breast cancer.

Neurodegeneration-Associated Proteins

• [TDP-43](/proteins/tdp-43) — RNA-binding protein aggregating in ALS/FTD. Loss of nuclear function contributes to disease.
• [FUS](/genes/fus) — TLS protein in ALS/FTD. Similar pathology to [TDP-43](/mechanisms/tdp-43-proteinopathy).
• [TARDBP](/proteins/tardbp) — gene encoding TDP-43. Over 50 mutations cause familial ALS.
• [SOD1](/proteins/sod1) — superoxide dismutase 1, mutated in familial ALS. First ALS gene discovered.
• [Huntingtin](/proteins/huntingtin) — mutant protein in Huntington's disease. Polyglutamine expansion causes toxicity.

Neuroinflammation Proteins

• [TREM2](/proteins/trem2) — triggering receptor on myeloid cells 2. AD risk variant (R47H) impairs [microglia](/cell-types/microglia-neuroinflammation) function.
• [CD33](/genes/cd33) — sialic acid-binding immunoglobulin-like lectin. Risk variant increases expression.
• [APOE](/proteins/apoe) — [apolipoprotein E](/proteins/apoe), major AD risk gene. APOE4 increases amyloid deposition.

Synaptic Proteins

• [Synuclein](/proteins/synuclein) — presynaptic protein in Lewy bodies. Normal function in synaptic vesicle regulation.
• [PSD-95](/proteins/psd-95) — postsynaptic density protein. Scaffold for excitatory synapses.
• [NMDA receptors](/proteins/nmda-receptor) — ionotropic glutamate receptors. Critical for synaptic plasticity.
• [AMPA receptors](/proteins/ampa-receptor) — ionotropic glutamate receptors. GluA2 subunit regulates calcium permeability.

Kinases and Phosphatases

• [GSK3β](/proteins/gsk3-beta) — glycogen synthase kinase 3 beta. Hyperactive in AD, phosphorylates tau.
• [CDK5](/proteins/cdk5) — cyclin-dependent kinase 5. Activator p25 drives pathological phosphorylation.
• [PP2A](/proteins/pp2a) — protein phosphatase 2A. Major tau phosphatase, activity reduced in AD.

Protein Function Categories

Protein Biomarkers

Many proteins serve as biomarkers for diagnosis and progression:

• NfL ([Neurofilament Light](/biomarkers/neurofilament-light-chain-nfl) Chain) — marker of axonal damage. Elevates in ALS, PD, AD.
• p-tau — tau phosphorylation state. Specific for AD vs other dementias.
• Neurogranin — synaptic dysfunction marker. Elevated in AD.
• YKL-40 — astrocyte activation. Non-specific inflammation marker.

Drug Targets

Key protein targets for therapeutic development:

• Amyloid-beta — monoclonal antibodies ([lecanemab](/entities/lecanemab), donanemab), vaccines
• Tau — monoclonal antibodies, kinase inhibitors (failed), aggregation inhibitors
• Alpha-synuclein — aggregation inhibitors, immunotherapy, ASO therapies
• BACE1 — [beta-secretase](/entities/bace1) inhibitor (failed due to side effects)
• [Gamma-secretase](/entities/gamma-secretase) — modulators (failed), not inhibitors

Protein Structure and Aggregation

Aggregation Mechanisms

Protein misfolding and aggregation follows a nucleation-dependent process:[@knowles2014]

Therapeutic Strategies

• Immunotherapy: Active vaccines or passive antibodies
• Small molecule inhibitors: Prevent aggregation or promote clearance
• Gene silencing: ASO or RNAi to reduce expression
• Enhance clearance: Promote [autophagy](/entities/autophagy) or [unfolded protein response](/entities/unfolded-protein-response)

Research Resources

• [Protein Rankings](/proteins/rankings) — protein targets by research activity
• [Protein Families](/proteins/protein-families) — grouped by function
• [Gene-Drug Interactions](/proteins/drug-targets) — drug development pathways

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

Topics

• [Proteins Overview](/proteins/overview) — This page
• [Proteins Rankings](/proteins/rankings) — Ranked list by research activity
• [Proteins Dashboard](/proteins/dashboard) — Data visualizations and metrics

Summary Statistics

• [Total Pages:* 3089 Proteins pages in this section](/proteins)
• [Last Updated:* This section is actively maintained](/genes/th)

A-Z All Pages

• [14-3-3 Proteins — Adapter and Scaffold Proteins](/proteins/14-3-3-protein)
• [26S Proteasome](/proteins/26s-proteasome)
• [3-Phosphoinositide Dependent Protein Kinase 1](/proteins/pdpk1-protein)
• [3R-Tau Protein](/proteins/3r-tau)
• [4E-BP1 Protein](/proteins/4e-bp1-protein)
• [4R-Tau Protein](/proteins/4r-tau)
• [5-HT1A Receptor Protein](/proteins/htr1a-protein)
• [5-HT1B Receptor Protein](/proteins/htr1b-receptor)
• [5-HT1E Receptor Protein](/proteins/htr1e-receptor)
• [5-HT2A Receptor](/proteins/serotonin-2a-receptor)
• [5-HT2A Receptor Protein](/proteins/5-ht2a-receptor)
• [5-HT2C Receptor](/proteins/serotonin-2c-receptor)
• [5-HT2C Receptor Protein](/proteins/htr2c-receptor)
• [5-HT4 Receptor Protein](/proteins/htr4-protein)
• [5-HT5A Receptor Protein](/proteins/htr5a-protein)
• [5-Hydroxytryptamine Receptor 1F (5-HT1F)](/proteins/htr1f-protein)
• [A-Raf Protein](/proteins/araf)
• [A2A Adenosine Receptor Protein](/proteins/a2a-adenosine-receptor)
• [A2M Protein](/proteins/a2m-protein)
• [ABCA1 Protein](/proteins/abcab1-protein)
• [ABCA1 Protein (ATP-binding Cassette Transporter A1)](/proteins/abca1-protein)
• [ABCA2 Protein](/proteins/abca2-protein)
• [ABCA4 Protein](/proteins/abcac4-protein)
• [ABCA7 Protein](/proteins/abca7-protein)
• [ABCB1 Protein (P-glycoprotein)](/proteins/abcb1-protein)
• [ABCD1 Protein](/proteins/abcd1-protein)
• [ABCD2 Protein](/proteins/abcd2-protein)
• [ABCD3 Protein](/proteins/abcd3)
• [ABCG1 Protein](/proteins/abcg1-protein)
• [ABCG2 Protein](/proteins/abcg2-protein)

References

Pathway Diagram

Pathway Diagram

The following diagram shows the key molecular relationships involving Proteins Overview discovered through SciDEX knowledge graph analysis: