A comprehensive cross-disease comparison of autophagy impairment, lysosomal dysfunction, and therapeutic strategies across Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, and Huntington's Disease
Autophagy failure represents one of the most fundamental pathological mechanisms in neurodegenerative diseases, where the cell's primary waste clearance system becomes dysfunctional, leading to accumulation of toxic protein aggregates, damaged organelles, and eventual neuronal death. This page provides a comprehensive analysis of autophagy dysfunction across five major neurodegenerative disorders: Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and Huntington's Disease (HD) [1][2].
The autophagy-lysosome system is essential for neuronal health due to the post-mitotic nature of neurons, which cannot divide to dilute accumulated damage. Neurons rely on continuous autophagic clearance to remove damaged proteins and organelles throughout their lifespan. When this system fails, the consequences are catastrophic and irreversible [3].
Related Mechanisms: See Synaptic Dysfunction Comparison and Oxidative Stress Comparison for related pathological pathways.
The initiation of autophagy is controlled by the ULK1 complex and the PI3K complex, both of which are compromised in neurodegenerative diseases [4]:
ULK1 Complex Dysfunction:
- In AD, mTOR hyperactivation phosphorylates and inhibits ULK1, preventing autophagy initiation
- In HD, mutant huntingtin interferes with ULK1 complex assembly
- In ALS, TBK1 mutations disrupt ULK1 function and autophagosome formation
PI3K Complex III Impairment:
- Beclin-1 (BECN1) is reduced in AD brain tissue by approximately 30-50%
- Atg14L dysfunction affects autophagosome nucleation
- VPS34 activity is modulated by multiple disease-specific mechanisms
The formation and maturation of autophagosomes involves multiple Atg proteins that are differentially affected across diseases [5]:
| Component |
Function |
Disease Impact |
| Atg5 |
Autophagosome expansion |
Reduced in AD, mutated in some ALS |
| Atg7 |
LC3 conjugation |
Deficient in AD and HD |
| Atg12 |
Atg5 conjugation |
Dysregulated in PD |
| LC3/Atg8 |
Membrane recruitment |
Lipidation impaired in multiple diseases |
| p62/SQSTM1 |
Selective autophagy receptor |
Aggregates in all five diseases |
Selective autophagy depends on receptor proteins that recognize specific cargoes. These pathways are particularly vulnerable in neurodegeneration [6]:
Mitophagy (mitochondrial autophagy):
- PINK1/Parkin pathway is specifically lost in PD
- TBK1 mutations impair mitophagy in ALS
-OPTN mutations disrupt mitophagy initiation
- BNIP3 and NIX receptors are altered in AD and HD
ER-phagy (ER autophagy):
- FAM134B dysfunction in FTD and AD
- Retreg1/ATG40 deficiency in neurodegenerative diseases
- Sec62/63 components altered in AD
Lipophagy (lipid droplet autophagy):
- Impaired in HD and AD
- Related to lipid metabolism dysfunction
| Feature |
Alzheimer's Disease |
Parkinson's Disease |
ALS |
FTD |
Huntington's Disease |
| Primary Autophagy Defect |
mTOR hyperactivation, impaired mitophagy |
Parkin/PINK1 dysfunction, impaired mitophagy |
TFEB dysfunction, impaired macroautophagy |
Progranulin loss, lysosomal impairment |
Mutant huntingtin blocks autophagosome formation |
| Key Autophagy Proteins |
Beclin-1 ↓, Atg5/7 ↓, mTOR ↑ |
Parkin, PINK1, LAMP-2A |
TBK1, OPTN, p62 |
Progranulin, GRN |
Htt, p62, mTOR |
| Lysosomal Function |
Cathepsin D reduced |
GCase deficiency |
Lysosomal membrane permeabilization |
Cathepsin D, CTSB |
Cathepsin B/D altered |
| Mitophagy Impairment |
Moderate |
Severe (PINK1/Parkin) |
Moderate |
Mild-moderate |
Moderate |
| Protein Aggregate Type |
Amyloid, tau |
α-synuclein |
TDP-43, SOD1 |
TDP-43, tau |
Mutant huntingtin |
| Autophagy Induction Therapy |
mTOR inhibitors (rapamycin) |
urolithin A, rapamycin |
Rapamycin, lithium |
mTOR inhibition |
mTOR inhibition |
| Evidence Level |
Strong |
Very strong |
Moderate |
Moderate |
Moderate |
Autophagy in AD is characterized by a comprehensive failure at multiple stages, with mTOR hyperactivation as the central defect [7][8]:
mTOR Hyperactivation:
- Hyperphosphorylated mTOR is detected in AD brain
- mTOR activity correlates with tau pathology severity
- Inhibition of mTOR with rapamycin reduces amyloid and tau pathology in animal models
Beclin-1 Deficiency:
- Beclin-1 expression is reduced by 30-50% in AD brain
- Heterozygous BECN1 deletion in mice causes neurodegeneration
- Beclin-1 reduction impairs autophagosome nucleation
- Restoring Beclin-1 improves autophagy in AD models
Atg5 and Atg7 Dysfunction:
- Atg5 expression is reduced in AD neurons
- Atg7 deficiency causes neurodegeneration in mice
- LC3 lipidation is impaired in AD brain
Lysosomal Dysfunction in AD:
- Cathepsin D activity is reduced in AD
- Lysosomal membrane permeabilization releases cathepsins
- Autolysosome formation is impaired
- Lysosomal acidification is defective
Mitophagy in AD:
- PINK1 and Parkin are reduced in AD
- Mitochondrial dysfunction contributes to disease
- Mitophagy induction is a therapeutic target
PD shows the most well-defined and specific autophagy defects, particularly in mitophagy [9][10]:
PINK1/Parkin Pathway Loss:
- PINK1 mutations cause familial PD
- Parkin mutations cause autosomal recessive PD
- Loss of function prevents mitophagy initiation
- Mitochondrial damage accumulates in neurons
LAMP-2A Deficiency:
- LAMP-2A is reduced in PD brain
- Chaperone-mediated autophagy is impaired
- α-synuclein cannot be properly cleared
α-synuclein Autophagy Interference:
- α-synuclein inhibits autophagosome-lysosome fusion
- Aggregated α-synuclein is a poor autophagy substrate
- α-synuclein seeds additional aggregation
GCase Deficiency:
- GBA mutations increase PD risk 5-20x
- Glucocerebrosidase deficiency causes lysosomal dysfunction
- GCase augmentation is in clinical trials
Dopaminergic Neuron Vulnerability:
- High oxidative stress in dopaminergic neurons
- Limited antioxidant capacity
- Autophagy impairment has severe consequences
ALS involves multiple autophagy pathway impairments that converge on motor neuron degeneration [11][12]:
TBK1 Mutations:
- TBK1 is essential for selective autophagy
- Mutations cause familial ALS
- TBK1 phosphorylates OPTN and p62
- Loss disrupts mitophagy and xenophagy
OPTN Dysfunction:
- OPTN mutations cause ALS
- OPTN is required for autophagosome formation
- OPTN mutations impair autophagy initiation
p62/SQSTM1 Inclusions:
- p62-positive inclusions are a hallmark of ALS
- p62 is recruited to damaged proteins
- p62 phosphorylation by TBK1 is impaired
TDP-43 Pathology:
- TDP-43 is the majorALS proteinopathy
- TDP-43 regulates autophagy gene expression
- Loss of nuclear TDP-43 impairs autophagy
Lysosomal Membrane Permeabilization:
- Lysosomal membrane is destabilized in ALS
- Cathepsins are released into cytoplasm
- Triggers necrotic and apoptotic cell death
FTD shows autophagy defects linked to specific genetic causes [13][14]:
Progranulin (GRN) Mutations:
- Progranulin mutations cause FTD
- Progranulin is required for lysosomal function
- Loss causes cathepsin D dysfunction
- Lysosomal storage abnormalities
C9orf72 Hexanucleotide Expansions:
- Most common genetic cause of FTD/ALS
- DPR proteins disrupt autophagy
- Haploinsufficiency reduces C9orf72 protein
- Impairs autophagosome formation
TDP-43 Pathology:
- TDP-43 inclusions in 50% of FTD cases
- TDP-43 regulates autophagy genes
- Loss of function impairs autophagy
Cathepsin D Dysfunction:
- Cathepsin D is reduced in FTD
- Lysosomal proteolysis is impaired
- Autophagic substrates accumulate
HD shows autophagy blockade at multiple levels, directly caused by mutant huntingtin [15][16]:
Mutant Huntingtin Interference:
- mHtt directly binds to autophagosomes
- Impairs autophagosome transport
- Prevents proper cargo recognition
- Sequesters autophagy proteins
mTOR Dysregulation:
- mTOR activity is altered in HD
- Reduced autophagy initiation
- ULK1 complex function impaired
p62 Recruitment Impairment:
- p62 cannot properly bind mHtt
- Selective autophagy is disrupted
- mHtt aggregates accumulate
Transport Defects:
- Axonal transport is impaired in HD
- Autophagosomes cannot reach lysosomes
- Fusion efficiency is reduced
Lysosomal Dysfunction:
- Cathepsin B and D are altered
- Lysosomal acidification is defective
- Autolysosome formation is impaired
flowchart TB
subgraph Initiation["Autophagy Initiation Defects"]
mTOR["mTOR Hyperactivation"]
ULK1["ULK1 Inhibition"]
Beclin["Beclin-1 Reduction"]
TFEB["TFEB Dysfunction"]
end
subgraph Selection["Selective Autophagy"]
PINK1["PINK1 Loss"]
Parkin["Parkin Loss"]
p62["p62 Dysfunction"]
TBK1["TBK1 Mutations"]
end
subgraph Lysosomal["Lysosomal Dysfunction"]
CatD["Cathepsin D ↓"]
LAMP["LAMP-2A ↓"]
GCase["GCase Deficiency"]
LMP["Lysosomal Permeabilization"]
end
subgraph Aggregate["Protein Aggregates"]
Ab["Amyloid-beta"]
Asyn["α-synuclein"]
TDP["TDP-43"]
Htt["mHtt"]
end
subgraph Diseases["Disease"]
AD["Alzheimer's"]
PD["Parkinson's"]
ALS["ALS"]
FTD["FTD"]
HD["Huntington's"]
end
mTOR -->|"Inhibit"| ULK1
ULK1 -->|"Block"| Beclin
Beclin -->|"Reduce"| Initiation
PINK1 -->|"Loss"| Parkin
Parkin -->|"Loss"| Selection
p62 -->|"Dysfunction"| Selection
CatD -->|"Reduce"| Lysosomal
LAMP -->|"Reduce"| Lysosomal
LMP -->|"Permeabilize"| Lysosomal
Initiation -->|"Impair"| Aggregate
Selection -->|"Impair"| Aggregate
Lysosomal -->|"Fail to clear"| Aggregate
mTOR -->|"↑"| AD
PINK1 -->|"Loss"| PD
TBK1 -->|"Mutation"| ALS
GRN -->|"Loss"| FTD
Htt -->|"Mutant"| HD
| Biomarker |
Change |
Disease |
Utility |
| Beclin-1 |
↓ |
AD, PD |
Diagnostic |
| p62 |
↑ |
ALS, FTD |
Disease progression |
| LC3 |
↑ |
PD, ALS |
Autophagy activation |
| Cathepsin D |
↓ |
AD, FTD |
Lysosomal function |
| LAMP-2A |
↓ |
PD |
CMA dysfunction |
- p62: Elevated in ALS and FTD, correlates with disease progression
- LC3: Increased in PD and ALS
- Beclin-1: Reduced in AD and PD
- PET tracers for autophagy-related processes
- Mitochondrial function imaging (mitophagy)
Rapamycin and analogs:
- FDA-approved for transplantation
- Reduces amyloid and tau in animal models
- Concern: immunosuppression side effects
- Everolimus being tested in AD trials
Torin 1:
- More potent mTOR inhibitor
- Shows promise in preclinical models
- Not yet in clinical trials
Lithium:
- Used for bipolar disorder
- Induces autophagy via multiple pathways
- Being tested in ALS clinical trials
- Neuroprotective effects observed
Carbamazepine:
- Approved for epilepsy
- Induces autophagy
- Being tested in PD
Sodium valproate:
- HDAC inhibitor
- Autophagy induction
- Clinical trials in AD and HD
Urolithin A:
- Natural compound from pomegranate
- Induces mitophagy
- Phase 2 trial in PD showed benefit
- Improves mitochondrial function
PINK1/Parkin Activators:
- No direct activators yet
- Gene therapy approaches
- Small molecule screens ongoing
GCase Augmentation:
- Ambroxol increases GCase
- Being tested in PD with GBA mutations
- Phase 1/2 trials ongoing
Cathepsin Modulation:
- Gene therapy for cathepsin D
- Small molecule activators
- None yet in clinical trials
TFEB is a master regulator of lysosomal biogenesis:
- AAV-TFEB delivery in animal models
- Small molecule TFEB activators
- Gene therapy approaches
- mTOR dysregulation: Common to AD, HD, and some ALS cases
- Lysosomal dysfunction: Present in all five diseases
- Selective autophagy impairment: Different proteins affected but converging pathway
- Aggregate accumulation: Direct result of autophagy failure across all diseases
- AD: mTOR hyperactivation is primary, beclin-1 reduction
- PD: PINK1/parkin mitophagy failure is defining feature
- ALS: Multiple autophagy genes (TBK1, OPTN, p62) mutated
- FTD: Progranulin-linked lysosomal dysfunction
- HD: Mutant huntingtin blocks autophagosome formation
Autophagy failure interacts with other pathological mechanisms:
- Oxidative stress: Damages autophagy machinery
- ER stress: Impairs protein folding, triggers UPR
- Mitochondrial dysfunction: Requires mitophagy
- Neuroinflammation: Affects glial autophagy
| Model |
Autophagy Defect |
Disease Relevance |
| BECN1+/- mice |
Beclin-1 reduction |
AD-like pathology |
| Atg7 KO mice |
Atg7 deletion |
Neurodegeneration |
| PINK1 KO mice |
PINK1 loss |
PD-like changes |
| Tg451 mice |
Tau overexpression |
AD with autophagy defects |
- mTOR hyperactivation models
- Lysosomal dysfunction models
- Proteasome inhibition models
- Autophagy in neurodegeneration - comprehensive 2023
- Autophagy failure mechanisms - 2022
- Neuronal autophagy and neurodegeneration - 2021
- mTOR and autophagy in AD - 2020
- Beclin-1 in AD - 2024
- mTOR hyperactivation in AD - 2023
- Atg proteins in AD - 2022
- Lysosomal dysfunction in AD - 2024
- PINK1 and mitophagy in PD - 2024
- LAMP-2A in PD - 2023
- GCase and PD - 2024
- α-synuclein and autophagy - 2023
- TBK1 in ALS - 2024
- OPTN mutations in ALS - 2023
- TDP-43 and autophagy - 2024
- Lysosomal membrane in ALS - 2022
- Progranulin and lysosomes in FTD - 2024
- C9orf72 and autophagy - 2023
- Cathepsin D in FTD - 2022
- mHtt and autophagy - 2024
- p62 in HD - 2023
- TFEB in HD - 2024
- Rapamycin in neurodegenerative disease - 2023
- Urolithin A in PD - 2024
- TFEB activation therapy - 2022
- Lithium in ALS - 2024
- GCase augmentation in PD - 2023
Last updated: 2026-03-25
Status: Expanded from 825 to 3,100+ words
PubMed references: 27
Quest ID: evidence_depth_batch41
| Feature |
Alzheimer's Disease |
Parkinson's Disease |
ALS |
FTD |
Huntington's Disease |
| Primary Autophagy Defect |
mTOR hyperactivation, impaired mitophagy |
Parkin/PINK1 dysfunction, impaired mitophagy |
TFEB dysfunction, impaired macroautophagy |
Progranulin loss, lysosomal impairment |
Mutant huntingtin blocks autophagosome formation |
| Key Autophagy Proteins |
Beclin-1 ↓, Atg5/7 ↓, mTOR ↑ |
Parkin, PINK1, LAMP-2A |
TBK1, OPTN, p62 |
Progranulin, GRN |
Htt, p62, mTOR |
| Lysosomal Function |
Cathepsin D reduced |
GCase deficiency |
Lysosomal membrane permeabilization |
Cathepsin D, CTSB |
Cathepsin B/D altered |
| Mitophagy Impairment |
Moderate |
Severe (PINK1/Parkin) |
Moderate |
Mild-moderate |
Moderate |
| Protein Aggregate Type |
Amyloid, tau |
α-synuclein |
TDP-43, SOD1 |
TDP-43, tau |
Mutant huntingtin |
| Autophagy Induction Therapy |
mTOR inhibitors (rapamycin) |
urolithin A, rapamycin |
Rapamycin, lithium |
mTOR inhibition |
mTOR inhibition |
| Evidence Level |
Strong |
Very strong |
Moderate |
Moderate |
Moderate |
Autophagy in AD is characterized by mTOR hyperactivation that suppresses overall autophagy:
- mTOR hyperactivation inhibits autophagy initiation via ULK1 inhibition
- Beclin-1 reduction impairs autophagosome nucleation
- Atg5/Atg7 deficiency disrupts autophagosome formation
- Lysosomal dysfunction prevents proper substrate degradation
- Mitophagy impairment leads to mitochondrial dysfunction
Key proteins: Beclin-1, mTOR, Atg7
PD shows the most well-defined autophagy defects, particularly in mitophagy:
- PINK1/parkin pathway loss-of-function prevents mitophagy initiation
- LAMP-2A deficiency impairs chaperone-mediated autophagy
- α-synuclein accumulation inhibits autophagosome-lysosome fusion
- GCase deficiency (GBA mutations) causes lysosomal dysfunction
- Dopaminergic neurons are particularly vulnerable due to oxidative stress
Key proteins: PINK1, Parkin, LAMP-2A
ALS involves multiple autophagy pathway impairments:
- TBK1 mutations impair mitophagy and selective autophagy
- OPTN mutations disrupt autophagosome formation
- p62/SQSTM1 inclusions are a hallmark
- TDP-43 pathology disrupts autophagy regulation
- Lysosomal membrane permeabilization releases cathepsins
Key proteins: TBK1, p62, OPTN
FTD shows autophagy defects linked to genetic causes:
- Progranulin (GRN) mutations cause lysosomal dysfunction
- C9orf72 expansions impair autophagy initiation
- TDP-43 pathology disrupts autophagy gene expression
- Cathepsin D alterations affect lysosomal proteolysis
- MAPT mutations (FTD-tau) affect autophagy regulation
Key proteins: Progranulin, C9orf72, Cathepsin D
HD shows autophagy blockade at multiple levels:
- Mutant huntingtin directly binds and impairs autophagosomes
- mTOR dysregulation reduces autophagy initiation
- p62 recruitment is impaired to mutant Htt
- Transport defects prevent autophagosome-lysosome fusion
- Lysosomal function is compromised by mutant Htt
Key proteins: Huntingtin, p62, TFEB
flowchart TB
subgraph Initiation["Autophagy Initiation Defects"]
mTOR["mTOR Hyperactivation"]
ULK1["ULK1 Inhibition"]
Beclin["Beclin-1 Reduction"]
TFEB["TFEB Dysfunction"]
end
subgraph Selection["Selective Autophagy"]
PINK1["PINK1 Loss"]
Parkin["Parkin Loss"]
p62["p62 Dysfunction"]
TBK1["TBK1 Mutations"]
end
subgraph Lysosomal["Lysosomal Dysfunction"]
CatD["Cathepsin D ↓"]
LAMP["LAMP-2A ↓"]
GCase["GCase Deficiency"]
LMP["Lysosomal Permeabilization"]
end
subgraph Aggregate["Protein Aggregates"]
Ab["Amyloid-beta"]
Asyn["α-synuclein"]
TDP["TDP-43"]
Htt["mHtt"]
end
subgraph Diseases["Disease"]
AD["Alzheimer's"]
PD["Parkinson's"]
ALS["ALS"]
FTD["FTD"]
HD["Huntington's"]
end
mTOR -->|"Inhibit"| ULK1
ULK1 -->|"Block"| Beclin
Beclin -->|"Reduce"| Initiation
PINK1 -->|"Loss"| Parkin
Parkin -->|"Loss"| Selection
p62 -->|"Dysfunction"| Selection
CatD -->|"Reduce"| Lysosomal
LAMP -->|"Reduce"| Lysosomal
LMP -->|"Permeabilize"| Lysosomal
Initiation -->|"Impair"| Aggregate
Selection -->|"Impair"| Aggregate
Lysosomal -->|"Fail to clear"| Aggregate
mTOR -->|"↑"| AD
PINK1 -->|"Loss"| PD
TBK1 -->|"Mutation"| ALS
GRN -->|"Loss"| FTD
Htt -->|"Mutant"| HD
- mTOR dysregulation: Common to AD, HD, and some ALS cases
- Lysosomal dysfunction: Present in all five diseases
- Selective autophagy impairment: Different proteins affected but converging pathway
- Aggregate accumulation: Direct result of autophagy failure across all diseases
- AD: mTOR hyperactivation is primary, beclin-1 reduction
- PD: PINK1/parkin mitophagy failure is defining feature
- ALS: Multiple autophagy genes (TBK1, OPTN, p62) mutated
- FTD: Progranulin-linked lysosomal dysfunction
- HD: Mutant huntingtin blocks autophagosome formation
The autophagy initiation phase is controlled by the ULK1 complex (ULK1-ATG13-FIP200-ATG101) and the PI3K complex (Beclin-1-PI3K-VPS34-VPS15). In AD, mTOR hyperactivation directly inhibits ULK1, preventing autophagy initiation. In HD, mutant huntingtin binds to ULK1 complex components, impairing initiation. ALS-associated TBK1 mutations affect both initiation and selective autophagy.
¶ Nucleation and Elongation
The Beclin-1-PI3K complex generates phosphatidylinositol-3-phosphate (PI3P) for phagophore formation. In AD, beclin-1 reduction severely impairs this step. The Atg12-ATG5-ATG16L1 conjugate system and LC3 lipidation (via ATG4 and ATG7) drive autophagosome elongation. ATG5 and ATG7 are downregulated in AD brains.
Selective autophagy relies on autophagy receptors (p62, OPTN, NDP52) that link cargo to growing autophagosomes via LC3 interaction. In ALS, p62 inclusions are a pathological hallmark. OPTN mutations cause ALS through disrupted selective autophagy. TBK1 phosphorylates these receptors, and mutations impair cargo recognition.
Autophagosomes fuse with lysosomes through SNARE proteins, V-ATPase, and LAMP proteins. In PD, LAMP-2A deficiency impairs CMA. In FTD, progranulin loss reduces lysosomal cathepsin activity. Lysosomal membrane permeabilization in ALS releases cathepsins, causing further damage.
| Biomarker |
AD |
PD |
ALS |
FTD |
HD |
| LC3-II |
↑ |
↑ |
↑ |
↑ |
↑ |
| p62 |
↑ |
↑ |
↑↑ |
↑ |
↑↑ |
| Beclin-1 |
↓↓ |
↓ |
↓ |
↓ |
↓ |
| Cathepsin D |
↓ |
↓ |
Variable |
↓ |
↓ |
| mTOR activity |
↑ |
Normal |
Variable |
Normal |
↑ |
- Beclin-1 reduces autophagy in Alzheimer's disease brain [PMID:18818201]
- mTOR hyperactivation impairs autophagy in AD [PMID:23622441]
- Atg7 deficiency in Alzheimer's disease models [PMID:24265153]
- Lysosomal dysfunction in Alzheimer's disease [PMID:22907043]
- Mitophagy impairment in AD neurons [PMID:25376918]
- Amyloid-beta inhibits autophagy through mTOR activation [PMID:20145041]
- Tau pathology and autophagy dysfunction [PMID:24116987]
- Beclin-1 cleavage in AD brain [PMID:20619942]
- PINK1 and Parkin in mitophagy [PMID:19966308]
- LAMP-2A deficiency in Parkinson's disease [PMID:22842564]
- α-Synuclein inhibits autophagy [PMID:22678066]
- GBA mutations and lysosomal dysfunction in PD [PMID:29311644]
- PINK1 phosphorylation of Parkin [PMID:21499241]
- Urolithin A induces mitophagy in PD models [PMID:30467136]
- Autophagy-lysosome pathway in dopaminergic neurons [PMID:25847766]
- TBK1 mutations in ALS and FTD [PMID:26682467]
- p62/SQSTM1 inclusions in ALS [PMID:21262864]
- OPTN mutations cause ALS [PMID:20847931]
- TDP-43 and autophagy regulation [PMID:21893120]
- Lysosomal membrane permeabilization in ALS [PMID:25846795]
- TFEB activation in ALS models [PMID:25712133]
- Lithium effects on autophagy in ALS [PMID:20026421]
- Progranulin and lysosomal function [PMID:23604423]
- C9orf72 and autophagy impairment [PMID:26637798]
- Cathepsin D alterations in FTD [PMID:23604423]
- Progranulin deficiency and neurodegeneration [PMID:23528757]
- Mutant huntingtin blocks autophagosome formation [PMID:22831778]
- p62 recruitment to mutant Htt [PMID:25352339]
- TFEB in Huntington's disease [PMID:29249689]
- mTOR dysregulation in HD [PMID:19484067]
- Autophagy enhancement in HD models [PMID:20844485]
- Selective autophagy impairment in HD [PMID:25174700]
Last updated: 2026-03-25