26a6d690a58883327b3853f6926e8a0f pmc_31731485.pdf 68c4d65cb4791295efc19e1650955bfcb3895d14 pmc_31731485.pdf bb6b0684227e85d4282d1b708a015dc0d8336745dcee968bb81b485597442ca4 pmc_31731485.pdf Title: Autophagic- and Lysosomal-Related Biomarkers for Parkinson’s Disease: Lights and Shadows Subject: Parkinson’s disease (PD) is a neurodegenerative disorder that currently affects 1% of the population over the age of 60 years, for which no disease-modifying treatments exist. This lack of effective treatments is related to the advanced stage of neurodegeneration existing at the time of diagnosis. Thus, the identification of early stage biomarkers is crucial. Biomarker discovery is often guided by the underlying molecular mechanisms leading to the pathology. One of the central pathways deregulated during PD, supported both by genetic and functional studies, is the autophagy-lysosomal pathway. Hence, this review presents different studies on the expression and activity of autophagic and lysosomal proteins, and their functional consequences, performed in peripheral human biospecimens. Although most biomarkers are inconsistent between studies, some of them, namely HSC70 levels in sporadic PD patients, and cathepsin D levels and glucocerebrosidase activity in PD patients carrying GBA mutations, seem to be consistent. Hence, evidence exists that the impairment of the autophagy-lysosomal pathway underlying PD pathophysiology can be detected in peripheral biosamples and further tested as potential biomarkers. However, longitudinal, stratified, and standardized analyses are needed to confirm their clinical validity and utility. Keywords: Parkinson’s disease; biomarker; autophagy; lysosome; glucocerebrosidase; alpha synuclein Author: Helena Xicoy, Núria Peñuelas, Miquel Vila and Ariadna Laguna Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.19 CreationDate: Fri Oct 25 11:39:30 2019 CEST ModDate: Fri Oct 25 11:39:30 2019 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1701092 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- UKPKIO+URWPalladioL-Ital Type 1 Custom yes yes no 104 0 MEHKCJ+URWPalladioL-Bold Type 1 Custom yes yes no 105 0 QTLELQ+Pxbsy Type 1 Builtin yes yes no 106 0 ENLEMO+VnURWPalladioL-Bold Type 1 Custom yes yes no 107 0 VGOZRJ+URWPalladioL-Roma Type 1 Custom yes yes no 108 0 OUMQKA+Pxsy Type 1 Builtin yes yes no 109 0 WOCYLK+Rpxr Type 1 Builtin yes yes no 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ぁふぴはばとちでどっぜ〴ぜ〰ぃちひではぜ〴ぜ〰いづぬどぶづひべぜ〲㍜〰げづぬちぴづつぜ〴ぜ〰ぐひはぴづどのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰がべびはびはねちぬぜ〴ぜ〰ぐひはぴづどのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸳⸱ Item: Title: がべびはびはねちぬぜ〴ぜ〰ぐひはぴづどのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸳⸱ Children: Item: Title: こぴひふっぴふひちぬぜ〴ぜ〰きづねぢひちのづぜ〴ぜ〰ぐひはぴづどのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸳⸲ Item: Title: ぅのぺべねづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いどひづっぴぜ〴ぜ〰きちひにづひびぜ〴ぜ〰はてぜ〴ぜ〰ぁふぴはばとちでどっ〭がべびはびはねちぬぜ〴ぜ〰うふのっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぅのぺべねちぴどっぜ〴ぜ〰ぁっぴどぶどぴどづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸱ Children: Item: Title: ぅのぺべねちぴどっぜ〴ぜ〰ぁっぴどぶどぴどづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸱ Children: Item: Title: ぇぬふっはっづひづぢひはびどつちびづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸲ Item: Title: ぇちぬちっぴはびどつちびづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸳ Item: Title: くぴとづひぜ〴ぜ〰がべびはびはねちぬぜ〴ぜ〰ぅのぺべねづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぎはの〭ぅのぺべねちぴどっぜ〴ぜ〰ぁびびちべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぎはの〭ぅのぺべねちぴどっぜ〴ぜ〰ぁびびちべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぉのつどひづっぴぜ〴ぜ〰きちひにづひびぜ〴ぜ〰はてぜ〴ぜ〰ぁふぴはばとちでどっ〭がべびはびはねちぬぜ〴ぜ〰うふのっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぁ〭こすぎぜ〴ぜ〰がづぶづぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰きどぴはばとちでべぜ〴ぜ〰きちひにづひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰がどばどつぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰ぉのてぬふづのっづつぜ〴ぜ〰ぢべぜ〴ぜ〰ぁふぴはばとちでべ〭げづぬちぴづつぜ〴ぜ〰ぐひはぴづどのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Children: Item: Title: ぁ〭こすぎぜ〴ぜ〰がづぶづぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰きどぴはばとちでべぜ〴ぜ〰きちひにづひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰がどばどつぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰ぉのてぬふづのっづつぜ〴ぜ〰ぢべぜ〴ぜ〰ぁふぴはばとちでべ〭げづぬちぴづつぜ〴ぜ〰ぐひはぴづどのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: きどぴはばとちでべぜ〴ぜ〰きちひにづひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰がどばどつぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰ぉのてぬふづのっづつぜ〴ぜ〰ぢべぜ〴ぜ〰ぁふぴはばとちでべ〭げづぬちぴづつぜ〴ぜ〰ぐひはぴづどのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: がどばどつぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰ぉのてぬふづのっづつぜ〴ぜ〰ぢべぜ〴ぜ〰ぁふぴはばとちでべ〭げづぬちぴづつぜ〴ぜ〰ぐひはぴづどのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡴慢汥⹣慰瑩潮⸴ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: QDCWHF+EURM10 FontSubset: true FirstChar: 11 LastChar: 12 FontDescriptor: FontName: QDCWHF+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true 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