PMID- 34830348 OWN - NLM STAT- MEDLINE DCOM- 20211217 LR - 20211217 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 22 DP - 2021 Nov 18 TI - Protein Misfolding and Aggregation: The Relatedness between Parkinson's Disease and Hepatic Endoplasmic Reticulum Storage Disorders. LID - 10.3390/ijms222212467 [doi] LID - 12467 AB - Dysfunction of cellular homeostasis can lead to misfolding of proteins thus acquiring conformations prone to polymerization into pathological aggregates. This process is associated with several disorders, including neurodegenerative diseases, such as Parkinson's disease (PD), and endoplasmic reticulum storage disorders (ERSDs), like alpha-1-antitrypsin deficiency (AATD) and hereditary hypofibrinogenemia with hepatic storage (HHHS). Given the shared pathophysiological mechanisms involved in such conditions, it is necessary to deepen our understanding of the basic principles of misfolding and aggregation akin to these diseases which, although heterogeneous in symptomatology, present similarities that could lead to potential mutual treatments. Here, we review: (i) the pathological bases leading to misfolding and aggregation of proteins involved in PD, AATD, and HHHS: alpha-synuclein, alpha-1-antitrypsin, and fibrinogen, respectively, (ii) the evidence linking each protein aggregation to the stress mechanisms occurring in the endoplasmic reticulum (ER) of each pathology, (iii) a comparison of the mechanisms related to dysfunction of proteostasis and regulation of homeostasis between the diseases (such as the unfolded protein response and/or autophagy), (iv) and clinical perspectives regarding possible common treatments focused on improving the defensive responses to protein aggregation for diseases as different as PD, and ERSDs. FAU - Padilla-Godinez, Francisco J AU - Padilla-Godinez FJ AD - Neurosciences Division, Cell Physiology Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico. AD - Regenerative Medicine Laboratory, Department of Surgery, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico. FAU - Ramos-Acevedo, Rodrigo AU - Ramos-Acevedo R AD - Neurosciences Division, Cell Physiology Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico. AD - Regenerative Medicine Laboratory, Department of Surgery, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico. FAU - Martinez-Becerril, Hilda Angelica AU - Martinez-Becerril HA AD - Neurosciences Division, Cell Physiology Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico. AD - Regenerative Medicine Laboratory, Department of Surgery, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico. FAU - Bernal-Conde, Luis D AU - Bernal-Conde LD AD - Neurosciences Division, Cell Physiology Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico. AD - Regenerative Medicine Laboratory, Department of Surgery, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico. FAU - Garrido-Figueroa, Jeronimo F AU - Garrido-Figueroa JF AD - Neurosciences Division, Cell Physiology Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico. AD - Regenerative Medicine Laboratory, Department of Surgery, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico. FAU - Hiriart, Marcia AU - Hiriart M AUID- ORCID: 0000-0001-5711-8868 AD - Neurosciences Division, Cell Physiology Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico. FAU - Hernandez-Lopez, Adriana AU - Hernandez-Lopez A AD - Regenerative Medicine Laboratory, Department of Surgery, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico. FAU - Arguero-Sanchez, Ruben AU - Arguero-Sanchez R AD - Regenerative Medicine Laboratory, Department of Surgery, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico. FAU - Callea, Francesco AU - Callea F AD - Department of Histopathology, Bugando Medical Centre, Catholic University of Healthy and Allied Sciences, Mwanza 1464, Tanzania. FAU - Guerra-Crespo, Magdalena AU - Guerra-Crespo M AD - Neurosciences Division, Cell Physiology Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico. AD - Regenerative Medicine Laboratory, Department of Surgery, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico. LA - eng GR - IN211419/DGAPA-PAPIIT/ GR - A1-S-10064/Consejo Nacional de Ciencia y Tecnologia/ PT - Journal Article PT - Review DEP - 20211118 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Coagulants) RN - 0 (Neuroprotective Agents) RN - 0 (Protease Inhibitors) RN - 0 (Protein Aggregates) RN - 0 (SERPINA1 protein, human) RN - 0 (SNCA protein, human) RN - 0 (alpha 1-Antitrypsin) RN - 0 (alpha-Synuclein) RN - 9001-32-5 (Fibrinogen) SB - IM MH - Afibrinogenemia/drug therapy/*genetics/metabolism/pathology MH - Animals MH - Autophagy/drug effects/genetics MH - Coagulants/therapeutic use MH - Endoplasmic Reticulum/drug effects/metabolism/pathology MH - Fibrinogen/*chemistry/genetics/metabolism MH - Gene Expression Regulation MH - Humans MH - Liver/metabolism/pathology MH - Neuroprotective Agents/therapeutic use MH - Parkinson Disease/drug therapy/*genetics/metabolism/pathology MH - Protease Inhibitors/therapeutic use MH - Protein Aggregates/drug effects MH - Protein Folding/drug effects MH - Unfolded Protein Response/drug effects MH - alpha 1-Antitrypsin/*chemistry/genetics/metabolism MH - alpha 1-Antitrypsin Deficiency/drug therapy/*genetics/metabolism/pathology MH - alpha-Synuclein/*chemistry/genetics/metabolism PMC - PMC8619695 OTO - NOTNLM OT - Parkinson's disease OT - alpha-1-antitrypsin OT - alpha-1-antitrypsin deficiency OT - alpha-synuclein OT - endoplasmic reticulum storage disease OT - fibrinogen OT - hereditary hypofibrinogenemia with hepatic storage OT - protein aggregation OT - protein misfolding COIS- The authors declare no conflict of interest. EDAT- 2021/11/28 06:00 MHDA- 2021/12/18 06:00 PMCR- 2021/11/18 CRDT- 2021/11/27 01:11 PHST- 2021/09/28 00:00 [received] PHST- 2021/10/18 00:00 [revised] PHST- 2021/10/19 00:00 [accepted] PHST- 2021/11/27 01:11 [entrez] PHST- 2021/11/28 06:00 [pubmed] PHST- 2021/12/18 06:00 [medline] PHST- 2021/11/18 00:00 [pmc-release] AID - ijms222212467 [pii] AID - ijms-22-12467 [pii] AID - 10.3390/ijms222212467 [doi] PST - epublish SO - Int J Mol Sci. 2021 Nov 18;22(22):12467. doi: 10.3390/ijms222212467.