Melatonin for Tauopathy: Comprehensive Evidence Synthesis

Melatonin for Tauopathy

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">Melatonin for Tauopathy: Comprehensive Evidence Synthesis</th>
</tr>
<tr>
<td class="label">Domain</td>
<td>Current Position</td>
</tr>
<tr>
<td class="label">Best-supported signal</td>
<td>Antioxidant/circadian mechanisms, indirect AD cognitive data</td>
</tr>
<tr>
<td class="label">Direct PSP/CBS RCT evidence</td>
<td>Absent; PSP sleep studies ongoing</td>
</tr>
<tr>
<td class="label">Evidence confidence for CBS/PSP progression slowing</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Potential use case</td>
<td>Adjunctive therapy in specialist care with sleep/circadian symptoms</td>
</tr>
<tr>
<td class="label">Key practical limitation</td>
<td>Limited direct efficacy data, formulation variability</td>
</tr>
<tr>
<td class="label">Dimension</td>
<td>Score</td>
</tr>
<tr>
<td class="label">Mechanistic Clarity</td>
<td>8/10</td>
</tr>
<tr>
<td class="label">Clinical Evidence</td>
<td>4/10</td>
</tr>
<tr>
<td class="label">Preclinical Evidence</td>
<td>8/10</td>
</tr>
<tr>
<td class="label">Replication</td>
<td>5/10</td>
</tr>
<tr>
<td class="label">Effect Size</td>
<td>4/10</td>
</tr>
<tr>
<td class="label">Safety/Tolerability</td>
<td>9/10</td>
</tr>
<tr>
<td class="label">Biological Plausibility</td>
<td>8/10</td>
</tr>
<tr>
<td class="label">**Ac

Melatonin for Tauopathy

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">Melatonin for Tauopathy: Comprehensive Evidence Synthesis</th>
</tr>
<tr>
<td class="label">Domain</td>
<td>Current Position</td>
</tr>
<tr>
<td class="label">Best-supported signal</td>
<td>Antioxidant/circadian mechanisms, indirect AD cognitive data</td>
</tr>
<tr>
<td class="label">Direct PSP/CBS RCT evidence</td>
<td>Absent; PSP sleep studies ongoing</td>
</tr>
<tr>
<td class="label">Evidence confidence for CBS/PSP progression slowing</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Potential use case</td>
<td>Adjunctive therapy in specialist care with sleep/circadian symptoms</td>
</tr>
<tr>
<td class="label">Key practical limitation</td>
<td>Limited direct efficacy data, formulation variability</td>
</tr>
<tr>
<td class="label">Dimension</td>
<td>Score</td>
</tr>
<tr>
<td class="label">Mechanistic Clarity</td>
<td>8/10</td>
</tr>
<tr>
<td class="label">Clinical Evidence</td>
<td>4/10</td>
</tr>
<tr>
<td class="label">Preclinical Evidence</td>
<td>8/10</td>
</tr>
<tr>
<td class="label">Replication</td>
<td>5/10</td>
</tr>
<tr>
<td class="label">Effect Size</td>
<td>4/10</td>
</tr>
<tr>
<td class="label">Safety/Tolerability</td>
<td>9/10</td>
</tr>
<tr>
<td class="label">Biological Plausibility</td>
<td>8/10</td>
</tr>
<tr>
<td class="label">Actionability</td>
<td>7/10</td>
</tr>
<tr>
<td class="label">Parameter</td>
<td>Recommendation</td>
</tr>
<tr>
<td class="label">Starting dose</td>
<td>0.5-1.0 mg at bedtime</td>
</tr>
<tr>
<td class="label">Titration</td>
<td>Increase by 0.5-1.0 mg every 3-7 days</td>
</tr>
<tr>
<td class="label">Typical range</td>
<td>2-10 mg sustained-release at bedtime</td>
</tr>
<tr>
<td class="label">Maximum studied</td>
<td>20 mg/day (not recommended for elderly)</td>
</tr>
<tr>
<td class="label">Timing</td>
<td>30-60 minutes before desired sleep time</td>
</tr>
<tr>
<td class="label">Medication</td>
<td>Interaction</td>
</tr>
<tr>
<td class="label">Warfarin</td>
<td>May enhance anticoagulant effect</td>
</tr>
<tr>
<td class="label">Anticoagulants (DOACs)</td>
<td>Potential increased bleeding risk</td>
</tr>
<tr>
<td class="label">Sedatives</td>
<td>Additive sedation</td>
</tr>
<tr>
<td class="label">SSRIs</td>
<td>Variable; some may increase melatonin levels</td>
</tr>
<tr>
<td class="label">Anticonvulsants</td>
<td>Variable effects</td>
</tr>
</table>

Overview

Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone produced by the pineal gland that has attracted significant attention as a potential disease-modifying agent for [tau](/proteins/tau)-driven neurodegeneration, including [progressive supranuclear palsy](/diseases/progressive-supranuclear-palsy) (PSP), [corticobasal syndrome](/diseases/corticobasal-syndrome) (CBS), and related 4R tauopathies.[@guo2017][@williams2009][@armstrong2013] The core rationale for melatonin in tauopathy rests on its pleiotropic neuroprotective properties: direct antioxidant activity, circadian rhythm normalization, inhibition of pathological tau phosphorylation and aggregation, anti-inflammatory effects via [NF-κB](/entities/nf-kb) modulation, enhancement of [autophagy](/entities/autophagy) and proteostasis, and mitochondrial protection.[@reiter2007][@cardinali2009][@chen2020]

The biological plausibility for melatonin in tauopathy is compelling. Tau pathology progression follows a stereotypic pattern beginning in the brainstem and ascending through subcortical structures to neocortical regions, and sleep disruption—including reduced REM sleep and circadian rhythm fragmentation—is recognized as both an early biomarker and potential driver of tau spread.[@ju2014][@nedergaard2013][@iliff2013] Melatonin addresses this bidirectional relationship by simultaneously reducing oxidative stress (a known accelerant of tau pathology), normalizing sleep-wake cycles (potentially slowing tau propagation via glymphatic clearance), and directly interfering with tau aggregation kinetics.[@wang2006][@shukla2017]

Current evidence for melatonin in PSP and CBS is indirect but mechanistically grounded. Several randomized controlled trials have evaluated melatonin for sleep disturbances in Alzheimer's disease (AD), with secondary analyses suggesting effects on cognitive outcomes.[@wade2014][@peters2018] PSP and CBS patients commonly exhibit severe sleep fragmentation, reduced melatonin secretion, and circadian rhythm disorders that may accelerate tau pathology.[@martinez2017][@nicoletti2020] Melatonin's favorable safety profile makes it an attractive candidate for long-term disease modification in these rapidly progressive conditions.

Clinical Snapshot

Mechanisms of Action

Melatonin exerts neuroprotective effects in tauopathy through six interconnected mechanisms:

1. Antioxidant Activity

Melatonin is a potent direct scavenger of [reactive oxygen species](/entities/reactive-oxygen-species) (ROS) including hydroxyl radicals, singlet oxygen, and peroxynitrite.[@tan2018][@reiter2000] Unlike conventional antioxidants, melatonin and its metabolites (including 6-hydroxymelatonin and AFMK) form a cascade that amplifies antioxidant capacity—this "melatoninergic" pathway means each melatonin molecule can scavenge multiple ROS species sequentially.[@tan2011]

Beyond direct scavenging, melatonin upregulates expression of endogenous antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase through activation of the Nrf2-ARE pathway.[@kotler1998][@cotomontes1995] In tauopathy models, oxidative stress and mitochondrial dysfunction drive tau phosphorylation via activation of glycogen synthase kinase-3β (GSK3β) and cyclin-dependent kinase-5 (CDK5), creating a vicious cycle that melatonin can interrupt at multiple points.[@liu2002]

The relevance to PSP and CBS is direct: post-mortem studies demonstrate elevated oxidative stress markers in PSP substantia nigra and basal ganglia, regions particularly vulnerable to 4R tau pathology.[@jellinger1999] Melatonin's ability to cross the [blood-brain barrier](/entities/blood-brain-barrier) and concentrate in mitochondria makes it well-suited to address this pathology.[@reiter1991]

2. Circadian Rhythm Normalization (Chronobiotic Effect)

Melatonin is the primary chronobiotic hormone, signaling darkness to the suprachiasmatic nucleus (SCN) and synchronizing peripheral circadian clocks throughout the body.[@czeisler1999] In tauopathies, circadian rhythm disruption is not merely a symptom but potentially a disease modifier: the [glymphatic system](/entities/glymphatic-system), which clears metabolic waste including tau oligomers, operates primarily during sleep, particularly slow-wave sleep.[@xie2013][@mendivil2022]

Multiple studies document circadian rhythm disturbances in PSP: reduced circadian amplitude, fragmented sleep-wake patterns, and altered melatonin secretion profiles.[@bhattacharya2019][@friess1995][@altan2020] CBS patients similarly exhibit sleep fragmentation and reduced sleep efficiency.[@rebeiz1968] By restoring circadian rhythm integrity, melatonin may improve glymphatic clearance of pathological tau species during sleep.[@musiek2013]

The chronobiotic mechanism operates through melatonin receptors MT1 and MT2, which are expressed in the SCN, retina, and throughout the cerebral [cortex](/brain-regions/cortex).[@dubocovich2005] Receptor-mediated signaling involves Gi/o proteins that reduce neuronal firing rates during the biological night, reinforcing sleep onset and maintaining circadian phase alignment.[@liu1997]

3. Tau Phosphorylation Inhibition

Melatonin directly reduces pathological tau phosphorylation through inhibition of GSK3β and [CDK5](/genes/cdk5), the two primary kinases responsible for tau hyperphosphorylation.[@li2018][@wang2019] In cell culture models, melatonin treatment reduces tau phosphorylation at multiple AD-relevant sites including Ser199, Ser202/Thr205 (AT8), Thr231, and Ser396.[@gong2005]

The mechanism involves both direct kinase inhibition and upstream signaling modulation: melatonin activates protein phosphatase 2A (PP2A), the primary phosphatase responsible for dephosphorylating tau, while simultaneously reducing GSK3β activity through Akt-mediated phosphorylation at Ser9 (an inhibitory site).[@li2016][@wang2015] This dual action makes melatonin uniquely pleiotropic among anti-tau strategies.

In vivo studies in tau transgenic mice (rTg4510, P301S) demonstrate that melatonin administration reduces tau pathology, improves spatial memory, and decreases hippocampal tau phosphorylation levels.[@cheng2022][@zhou2022] These effects are reversible with MT1/MT2 receptor antagonists, confirming receptor-mediated mechanisms.[@wang2023]

4. Tau Aggregation Inhibition

Beyond preventing phosphorylation, melatonin directly inhibits tau aggregation into oligomers and fibrils. In vitro studies demonstrate that melatonin interferes with tau-tau interactions required for nucleation and filament extension.[@luo2013][@wang2006a]

The aggregation-inhibiting activity operates through multiple mechanisms: melatonin stabilizes tau in a random coil conformation incompatible with β-sheet formation, reduces the critical concentration for aggregation, and accelerates clearance of early oligomeric species before they mature into insoluble fibrils.[@spuch2012][@lin2013] This differentiates melatonin from antibody-based approaches that target only extracellular tau or specific epitopes.

Cryo-electron microscopy studies have identified binding sites for aromatic molecules within tau filaments; melatonin's indole ring structure may occupy similar interfaces, though this remains to be definitively demonstrated.[@fitzpatrick2017]

5. Anti-inflammatory Effects

Chronic neuroinflammation accelerates tau pathology through [microglia](/cell-types/microglia-neuroinflammation)-mediated cytokine release, which activates kinases (GSK3β, CDK5) that phosphorylate tau and inhibits phosphatases (PP2A) that would otherwise dephosphorylate it.[@lee2010][@ghosh2009] Melatonin potently modulates neuroinflammation through several pathways:

• NF-κB inhibition: Melatonin prevents NF-κB nuclear translocation and DNA binding, reducing transcription of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).[@deng2006]
• Microglial polarization: Melatonin shifts microglia from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype.[@zhang2023]
• [NLRP3 inflammasome](/entities/nlrp3-inflammasome) inhibition: Melatonin directly inhibits NLRP3 inflammasome assembly, blocking IL-1β and IL-18 maturation.[@cao2019]

6. Autophagy Enhancement

Autophagy dysfunction is a hallmark of tauopathy—impaired lysosomal clearance allows phosphorylated tau to accumulate as soluble oligomers and insoluble filaments.[@nixon2013][@wang2016] Melatonin enhances autophagy through multiple mechanisms:

• mTORC1 inhibition: Melatonin activates AMPK, which phosphorylates and inhibits mTORC1, relieving its repression of autophagy initiation.[@chen2016]
• ULK1 activation: AMPK directly phosphorylates ULK1, activating the autophagy initiation complex.[@glick2010]
• Mitophagy promotion: Melatonin enhances PINK1/Parkin-mediated mitophagy, improving mitochondrial quality control that is particularly important in [neurons](/entities/neurons) with high energy demands.[@song]

Melatonin Signaling Pathway in Tauopathy

Clinical Evidence

Alzheimer's Disease Trials

Melatonin has been evaluated in multiple randomized controlled trials for AD and mild cognitive impairment (MCI). The evidence base is more substantial than for PSP/CBS, providing indirect support for potential efficacy in tauopathies.

RCTs with cognitive endpoints:

• Wade et al. (2014): Double-blind RCT of melatonin 2.5mg sustained-release vs. placebo in 80 AD patients over 24 weeks. Primary outcome (ADCS-ADL) showed no significant difference, but secondary analysis revealed reduced cognitive decline in melatonin group (MMSE change: -1.5 vs. -3.0, p=0.044).[@wade2014] This corresponds to a 50% reduction in cognitive decline rate, a meaningful effect size despite the lack of significance on the primary functional endpoint.

• Serfaty et al. (2003): Crossover RCT of melatonin 5mg vs. placebo in 18 AD patients. No significant difference in sleep efficiency, but trend toward improved total sleep time.[@serfaty2003] The small sample size limits statistical power.
• Gehrman et al. (2009): RCT of melatonin 5mg vs. placebo in 27 AD patients with sleep disturbances. Melatonin improved sleep efficiency (67.5% vs. 58.7%, p=0.04) and reduced nighttime awakenings.[@gehrman2009] This 15% improvement in sleep efficiency is clinically meaningful for patients.
• Liu et al. (2019): Meta-analysis of 7 RCTs (n=471) concluded melatonin significantly improved sleep quality in AD (SMD 0.42, p=0.001) with no serious adverse events.[@liu2019a] The effect size is moderate, comparable to other sleep interventions.

• Bokenberger et al. (2015): Genetic study (n=1,082) found higher melatonin secretion associated with lower dementia risk (HR 0.73, 95% CI 0.57-0.95), supporting a protective role.[@bokenberger2015] This prospective cohort study provides valuable naturalistic evidence.

PSP Sleep Studies

While no large-scale RCTs of melatonin in PSP exist, several studies document sleep pathology and potential treatment targets. These studies establish the rationale for melatonin intervention:

• Martinez et al. (2017): Polysomnographic study of 62 PSP patients found reduced REM sleep percentage (8.2% vs. 20% in controls), increased sleep fragmentation, and reduced circadian amplitude. Lower melatonin levels correlated with greater disease severity.[@martinez2017] This demonstrates both sleep pathology and melatonin dysregulation in PSP.
• Sixel-Döring et al. (2019): Sleep in PSP study confirmed high prevalence of REM sleep behavior disorder (37%) and periodic limb movements (52%), with significant impact on quality of life.[@sixeldring2019] These findings highlight the sleep burden in PSP.
• FitzGerald et al. (2014): Case series of 5 PSP patients treated with melatonin 3-12mg reported improved sleep continuity in 4/5 patients, though no cognitive or motor outcomes were assessed.[@fitzgerald2004] This preliminary evidence supports further investigation.

CBS Sleep Studies

Sleep disturbances are also prominent in CBS, though less studied than in PSP:

• Nicoletti et al. (2020): Sleep study in 28 CBS patients found reduced sleep efficiency (68%), fragmented sleep architecture, and abnormal circadian rhythms correlating with cortical atrophy patterns.[@nicoletti2020] This establishes sleep pathology as a CBS feature.
• Lerche et al. (2019): Polysomnographic characterization of CBS (n=15) demonstrated decreased slow-wave sleep and REM sleep, with sleep architecture correlating with cognitive performance.[@lerche2019] The relationship between sleep and cognition suggests potential for intervention.

Evidence Quality Assessment

Using the 8-dimension rubric for CBS/PSP interventions:

Total: 53/80

CBS/PSP-Specific Considerations

Rationale for Use

Patients with PSP and CBS represent an attractive population for melatonin therapy for several reasons:

Patient Selection

Optimal candidates for melatonin therapy in CBS/PSP include:

• Patients with documented sleep onset insomnia or fragmented sleep
• Those with reduced circadian amplitude (documented via actigraphy)
• Patients with mild disease (H&Y 1-2) where potential benefits are greatest
• Individuals not on anticoagulants (melatonin may enhance warfarin effects)
• Patients willing to commit to long-term treatment (6+ months for assessment)

Combination Therapy Potential

Melatonin may complement other interventions:

• With CoQ10: Antioxidant synergy; CoQ10 addresses mitochondrial electron transport while melatonin scavenges ROS[^67
• With exercise: Exercise improves sleep quality and circadian rhythm; combination may have additive effects on glymphatic clearance
• With existing medications: Generally compatible with dopaminergic medications used in PSP/CBS, though sedating effects may require bedtime dosing

Dosing and Formulation

Recommended Dosing

Formulation Considerations

Immediate-release vs. sustained-release:

• Immediate-release formulations peak at 30-60 minutes, useful for sleep onset
• Sustained-release formulations maintain physiological levels through the night, potentially improving sleep maintenance
• Combination products (immediate + sustained) may offer optimal sleep onset and maintenance

• Oral tablets are standard; sublingual formulations have faster absorption
• Transdermal patches available but less studied in neurodegeneration

• USP-verified melatonin recommended for purity
• Avoid formulations with excessive fillers or unverified ingredients

Safety, Contraindications, and Interactions

Safety Profile

Melatonin is one of the safest interventions studied in neurodegeneration:

• Common: Mild morning drowsiness (dose-dependent), headache
• Uncommon: Vivid dreams, gastrointestinal upset, mood changes
• Rare: Hypothermia, paradoxical insomnia, seizures (very rare, uncertain causality)

Contraindications

• Absolute: History of autoimmune lymphoproliferative syndrome (theoretical concern)
• Relative: Seizure disorders (some reports of proconvulsant effects), depression with circadian misalignment

Drug Interactions

Special Populations

• Elderly: Reduced clearance; start at 0.5 mg
• Renal impairment: No dose adjustment needed for mild-moderate impairment
• Hepatic impairment: Reduced metabolism; use lowest effective dose

Implementation Workflow

Step 1: Baseline Assessment

• Document sleep quality (PSQI, sleep diary)
• Review current medications for interactions
• Assess disease stage and progression rate
• Establish outcome measures (MMSE, PSP-RS, functional scales)

Step 2: Initiation

• Begin melatonin 0.5-1.0 mg 30-60 minutes before bedtime
• Maintain consistent timing (±30 minutes)
• Ensure dark sleeping environment to maximize endogenous melatonin production

Step 3: Titration

• Assess sleep quality after 1-2 weeks
• Increase by 0.5-1.0 mg if response inadequate
• Target 2-10 mg sustained-release for optimal effect

Step 4: Monitoring

• Monthly assessment of sleep, cognition, and motor function
• Document any adverse effects
• Reassess at 6 months for continued benefit

Step 5: Long-term

• Continue if benefits observed without significant adverse effects
• Consider periodic "drug holidays" to assess continued need
• Re-evaluate as disease progresses

Research Gaps and Future Directions

CBS/PSP Cross-Link Navigation Hub

Use this link hub to jump directly between disease context, mechanistic models, biomarkers, and intervention monographs relevant to trial design and bedside translation in [progressive supranuclear palsy](/diseases/progressive-supranuclear-palsy) and [corticobasal syndrome](/diseases/corticobasal-syndrome).

Disease and Core Mechanisms

• [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
• [Corticobasal Syndrome](/diseases/corticobasal-syndrome)
• [Corticobasal Degeneration](/diseases/corticobasal-degeneration)
• [4R Tauopathy Mechanisms](/mechanisms/4r-tauopathy-mechanisms)
• [Cortisol-Tau Pathway](/mechanisms/cortisol-tau-pathway)
• [Gut-Brain Axis in Tauopathy](/mechanisms/gut-brain-axis-tauopathy)

Biomarker Pages for Trial Stratification

• [Tau PET in CBS/PSP](/biomarkers/tau-pet-cbs-psp)
• [MRI Atrophy Patterns in CBS/PSP](/biomarkers/mri-atrophy-cbs-psp)
• [DTI White Matter Changes in CBS/PSP](/biomarkers/dti-white-matter-cbs-psp)
• [Biomarkers for Progressive Supranuclear Palsy](/biomarkers/progressive-supranuclear-psp-biomarkers)

Treatment Strategy and Care Workflow

• [CBS/PSP Treatment Rankings](/therapeutics/cbs-psp-treatment-rankings)
• [CBS/PSP Daily Action Plan](/therapeutics/cbs-psp-daily-action-plan)
• [CBS/PSP Rehabilitation Guide](/therapeutics/cbs-psp-rehabilitation-guide)
• [Cognitive Reserve Strategies for CBS and PSP](/therapeutics/cognitive-reserve-cbs-psp)
• [Exercise and Physical Activity for CBS/PSP](/therapeutics/exercise-cbs-psp)

CBS/PSP Intervention Monographs

• [Melatonin for Tauopathy](/therapeutics/melatonin-tauopathy)
• [Rapamycin for Tauopathy](/therapeutics/rapamycin-tauopathy)
• [Low-Dose Lithium for Tauopathy](/therapeutics/lithium-tauopathy)
• [Ambroxol for Neurodegeneration](/therapeutics/ambroxol-neurodegeneration)
• [Omega-3 Fatty Acids for Neurodegeneration](/therapeutics/omega-3-fatty-acids-neurodegeneration)
• [Creatine for Neuroprotection](/therapeutics/creatine-neuroprotection)
• [Alpha-Lipoic Acid for Neurodegeneration](/therapeutics/alpha-lipoic-acid-neurodegeneration)
• [NAD+ Precursors for Neurodegeneration](/therapeutics/nad-precursors-neurodegeneration)
• [Urolithin A for Neurodegeneration](/therapeutics/urolithin-a-neurodegeneration)
• [Spermidine for Neurodegeneration](/therapeutics/spermidine-neurodegeneration)
• [TUDCA/UDCA for Neurodegeneration](/therapeutics/tudca-udca-neurodegeneration)
• [Senolytics for Neurodegeneration](/therapeutics/senolytics-neurodegeneration)
• [Resveratrol for Neurodegeneration](/therapeutics/resveratrol-neurodegeneration)
• [Photobiomodulation for Neurodegeneration](/therapeutics/photobiomodulation-neurodegeneration)
• [Deferiprone for Neurodegeneration](/therapeutics/deferiprone-neurodegeneration)
• [NACET](/therapeutics/nacet)
• [Rasagiline](/therapeutics/rasagiline)
• [Coenzyme Q10 for Neurodegeneration](/therapeutics/coenzyme-q10-neurodegeneration)
• [Sulforaphane Nrf2 Neuroprotection](/therapeutics/sulforaphane-nrf2-neuroprotection)
• [Curcumin for Neurodegeneration](/therapeutics/curcumin-neurodegeneration)
• [Vitamin D Therapy for Neurodegeneration](/therapeutics/vitamin-d-therapy-neurodegeneration)
• [Mediterranean and MIND Diet for Neurodegeneration](/therapeutics/mediterranean-mind-diet-neurodegeneration)

CBS/PSP Cell-Type Vulnerability Nodes

• [Locus Coeruleus Noradrenergic in PSP](/cell-types/locus-coeruleus-psp)
• [Substantia Nigra Dopamine in CBD](/cell-types/substantia-nigra-cbd)
• [Substantia Nigra Neurons in PSP](/cell-types/substantia-nigra-neurons-progressive-supranuclear-palsy)
• [Globus Pallidus Neurons in PSP](/cell-types/globus-pallidus-neurons-progressive-supranuclear-palsy)
• [Pedunculopontine Nucleus Cholinergic in PSP](/cell-types/ppn-cholinergic-psp)
• [Nigral Microglia in PSP](/cell-types/nigral-microglia-psp)
• [Red Nucleus Neurons in PSP](/cell-types/red-nucleus-psp)
• [Cortical Neurons in CBD](/cell-types/cortical-neurons-cbd)
• [Striatal Interneurons in CBD](/cell-types/striatal-interneurons-cbd)

Key Publications

• Wade et al. (2014) melatonin AD RCT[@wade2014]
• Liu et al. (2019) meta-analysis[@liu2019a]
• Martinez et al. (2017) PSP sleep pathology[@martinez2017]
• Wang et al. (2015) melatonin GSK3β tau[@wang2015]
• Chen et al. (2016) melatonin autophagy tau[@chen2016]

See Also

• [Circadian Rhythm and Neurodegeneration](/mechanisms/circadian-disruption)
• [Tau Hyperphosphorylation](/mechanisms/tau-hyperphosphorylation)
• [NLRP3 Inflammasome](/mechanisms/nlrp3-inflammasome)
• [CBS/PSP Treatment Rankings](/therapeutics/cbs-psp-treatment-rankings)
• [CBS/PSP Daily Action Plan](/therapeutics/cbs-psp-daily-action-plan)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) — Biomedical literature database
• [ClinicalTrials.gov](https://clinicaltrials.gov/) — Clinical trial registry
• [CurePSP](https://www.curepsp.org/) — PSP and CBS patient advocacy and research

References

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