{"id":280279,"date":"2024-07-31T09:00:21","date_gmt":"2024-07-31T07:00:21","guid":{"rendered":"https:\/\/dhcp205002.cbm.uam.es\/?page_id=280279"},"modified":"2024-12-09T09:26:33","modified_gmt":"2024-12-09T08:26:33","slug":"pathogenic-mechanisms-of-alzheimers-disease","status":"publish","type":"page","link":"https:\/\/www.cbm.uam.es\/index.php\/scientific-programs\/physiological-and-pathological-processes\/molecular-neuropathology\/pathogenic-mechanisms-of-alzheimers-disease\/","title":{"rendered":"Pathogenic mechanisms of Alzheimer\u2019s disease"},"content":{"rendered":"<p>[et_pb_section fb_built=&#8221;1&#8243; _builder_version=&#8221;4.27.0&#8243; _module_preset=&#8221;default&#8221; background_color=&#8221;#34609B&#8221; background_image=&#8221;https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/07\/iStock-1356994685small-scaled.jpg&#8221; background_position=&#8221;bottom_center&#8221; background_vertical_offset=&#8221;32%&#8221; min_height=&#8221;352px&#8221; height=&#8221;294px&#8221; da_disable_devices=&#8221;off|off|off&#8221; global_colors_info=&#8221;{}&#8221; da_is_popup=&#8221;off&#8221; da_exit_intent=&#8221;off&#8221; da_has_close=&#8221;on&#8221; da_alt_close=&#8221;off&#8221; da_dark_close=&#8221;off&#8221; da_not_modal=&#8221;on&#8221; da_is_singular=&#8221;off&#8221; da_with_loader=&#8221;off&#8221; da_has_shadow=&#8221;on&#8221;][et_pb_row column_structure=&#8221;2_5,3_5&#8243; use_custom_gutter=&#8221;on&#8221; gutter_width=&#8221;4&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; background_color=&#8221;RGBA(255,255,255,0)&#8221; custom_margin=&#8221;61px||||false|false&#8221; custom_padding=&#8221;||0px|||&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;2_5&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; background_color=&#8221;rgba(52,96,155,0.83)&#8221; custom_padding=&#8221;50px||50px|50px|false|false&#8221; border_radii=&#8221;on|15px|15px|15px|15px&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_text _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; text_text_color=&#8221;#FFFFFF&#8221; custom_margin=&#8221;0px||10px||false|false&#8221; custom_padding=&#8221;0px||0px||false|false&#8221; global_colors_info=&#8221;{}&#8221;]<\/p>\n<p>Scientific Program<\/p>\n<p>[\/et_pb_text][et_pb_heading title=&#8221;Physiological and pathological processes&#8221; _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; title_font=&#8221;Montserrat||||||||&#8221; title_text_color=&#8221;#FFFFFF&#8221; title_font_size=&#8221;43px&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_heading][\/et_pb_column][et_pb_column type=&#8221;3_5&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; custom_padding=&#8221;157px||||false|false&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_text _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;]<\/p>\n<h4 style=\"text-align: center;\"><span style=\"color: #13b5bd;\">UNITS IN THIS PROGRAM<br \/>\n<\/span><\/h4>\n<hr \/>\n<h6 style=\"text-align: center;\"><span style=\"color: #13b5bd;\"><br \/>\n<a href=\"\/index.php\/scientific-programs\/physiological-and-pathological-processes\/molecular-neuropathology\/\">Molecular neuropathology<\/a><\/span>\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0<span style=\"color: #abb8c3;\"><a href=\"\/index.php\/scientific-programs\/physiological-and-pathological-processes\/metabolic-and-signaling-networks-in-disease\/\">Metabolic and signaling networks in disease<\/a><\/span><\/h6>\n<p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=&#8221;1&#8243; 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da_with_loader=&#8221;off&#8221; da_has_shadow=&#8221;on&#8221;][et_pb_row column_structure=&#8221;1_4,3_4&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;1_4&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_image src=&#8221;\/imgs\/52.jpg&#8221; title_text=&#8221;logoRecurso 7&#8243; align=&#8221;right&#8221; module_class=&#8221;roundedImg&#8221; _builder_version=&#8221;4.27.0&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_image][\/et_pb_column][et_pb_column type=&#8221;3_4&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_heading title=&#8221;Mar\u00eda Jes\u00fas Bullido G\u00f3mez-Heras&#8221; _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; title_level=&#8221;h3&#8243; title_text_align=&#8221;left&#8221; title_text_color=&#8221;#008C93&#8243; global_colors_info=&#8221;{}&#8221;][\/et_pb_heading][et_pb_text _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; custom_margin=&#8221;-27px||||false|false&#8221; link_option_url_new_window=&#8221;on&#8221; global_colors_info=&#8221;{}&#8221;]<\/p>\n<p style=\"text-align: left;\">\n<a href=\"https:\/\/www.ciberned.es\/grupos\/grupo-de-investigacion?id=28805\" target=\"blank\" rel=\"noopener\">External group website<\/a><br \/>\n<a href=\"https:\/\/orcid.org\/0000-0002-6477-1117\" target=\"blank\" rel=\"noopener\">ORCID<\/a><\/p>\n<p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=&#8221;1&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; background_color=&#8221;#13B5BD&#8221; custom_margin=&#8221;0px||0px||false|false&#8221; custom_padding=&#8221;0px||0px||false|false&#8221; da_disable_devices=&#8221;off|off|off&#8221; global_colors_info=&#8221;{}&#8221; da_is_popup=&#8221;off&#8221; da_exit_intent=&#8221;off&#8221; da_has_close=&#8221;on&#8221; da_alt_close=&#8221;off&#8221; da_dark_close=&#8221;off&#8221; da_not_modal=&#8221;on&#8221; da_is_singular=&#8221;off&#8221; da_with_loader=&#8221;off&#8221; da_has_shadow=&#8221;on&#8221;][et_pb_row column_structure=&#8221;1_3,1_3,1_3&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;1_3&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_button button_url=&#8221;#investiga&#8221; button_text=&#8221;Research&#8221; button_alignment=&#8221;center&#8221; _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; custom_button=&#8221;on&#8221; button_bg_color=&#8221;#34609B&#8221; animation_style=&#8221;zoom&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_button][\/et_pb_column][et_pb_column type=&#8221;1_3&#8243; 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_builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; background_enable_image=&#8221;off&#8221; background_size=&#8221;custom&#8221; background_image_height=&#8221;84%&#8221; background_position=&#8221;bottom_right&#8221; custom_margin=&#8221;0px||0px||false|false&#8221; custom_padding=&#8221;0px||15px||false|false&#8221; da_disable_devices=&#8221;off|off|off&#8221; global_colors_info=&#8221;{}&#8221; da_is_popup=&#8221;off&#8221; da_exit_intent=&#8221;off&#8221; da_has_close=&#8221;on&#8221; da_alt_close=&#8221;off&#8221; da_dark_close=&#8221;off&#8221; da_not_modal=&#8221;on&#8221; da_is_singular=&#8221;off&#8221; da_with_loader=&#8221;off&#8221; da_has_shadow=&#8221;on&#8221;][et_pb_row column_structure=&#8221;1_2,1_2&#8243; use_custom_gutter=&#8221;on&#8221; gutter_width=&#8221;2&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; custom_margin=&#8221;20px||||false|false&#8221; custom_padding=&#8221;||||false|false&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;1_2&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_text admin_label=&#8221;resumen&#8221; module_id=&#8221;resumen&#8221; module_class=&#8221;resumen&#8221; _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; text_font_size=&#8221;15px&#8221; text_line_height=&#8221;1.8em&#8221; background_color=&#8221;#f1f8fe&#8221; custom_padding=&#8221;20px|20px|20px|20px|true|false&#8221; border_width_top=&#8221;1px&#8221; border_color_top=&#8221;#008C93&#8243; border_width_bottom=&#8221;1px&#8221; border_color_bottom=&#8221;#008C93&#8243; global_colors_info=&#8221;{}&#8221;]<\/p>\n<p style=\"text-align: justify;\">Our team studies the mechanisms connecting Alzheimer\u2019s disease, the most common form of dementia, with the highly prevalent virus Herpes Simplex I. We develop models derived from human multipotent cells to assess these mechanisms, and perform clinical studies to validate our findings. With this strategy, we also aim to identify new biomarkers and therapeutic targets for this complex disease.<\/p>\n<p>[\/et_pb_text][\/et_pb_column][et_pb_column type=&#8221;1_2&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; custom_padding=&#8221;||||false|false&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_image src=&#8221;https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/06\/LUH-BC-BTub-KI67-1-Mariaje-Bullido.jpg&#8221; title_text=&#8221; &#8221; _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; animation_style=&#8221;zoom&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_image][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=&#8221;3_5,2_5&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; custom_margin=&#8221;||||false|false&#8221; custom_padding=&#8221;0px||||false|false&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;3_5&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_heading title=&#8221;Research&#8221; module_id=&#8221;investiga&#8221; _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; custom_margin=&#8221;0px|||0px|false|false&#8221; custom_padding=&#8221;3px|||8px|false|false&#8221; border_width_left=&#8221;6px&#8221; border_color_left=&#8221;#34609B&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_heading][et_pb_text _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;]<\/p>\n<p style=\"text-align: justify;\">To identify genes and mechanisms involved in the neurodegeneration characteristic of Alzheimer&#8217;s disease (AD), we developed cell models that reflect different aspects of the pathogenesis of the disease. These models allow us to identify new genes\/functions associated with AD, which could be therapeutic targets for the disease. To do this, we analyze differential gene expression in the models and develop genetic association studies and biomarkers in clinical samples. In recent years, we have focused on models of herpes simplex virus 1 (HSV-1) infection that present characteristic markers of AD, including alterations in the trafficking, metabolism and proteolysis of the amyloid precursor protein (APP), as well as in the phosphorylation of the tau protein.<\/p>\n<p>[\/et_pb_text][\/et_pb_column][et_pb_column type=&#8221;2_5&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_image src=&#8221;https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/12\/2024-04-17-Grupo-MJ-Bullido-1000px.jpg&#8221; title_text=&#8221;2024-04-17 Grupo MJ Bullido-1000px&#8221; _builder_version=&#8221;4.27.3&#8243; _module_preset=&#8221;default&#8221; custom_margin=&#8221;60px||||false|false&#8221; custom_padding=&#8221;|||27px||&#8221; animation_style=&#8221;zoom&#8221; hover_enabled=&#8221;0&#8243; border_width_all=&#8221;3px&#8221; border_color_all=&#8221;#13B5BD&#8221; box_shadow_style=&#8221;preset3&#8243; global_colors_info=&#8221;{}&#8221; sticky_enabled=&#8221;0&#8243;][\/et_pb_image][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; custom_padding=&#8221;0px||||false|false&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;4_4&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_text _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;]<\/p>\n<p style=\"text-align: justify;\">The study of the lysosome autophagy pathway in these models indicates that HSV-1, especially in the presence of oxidative stress, profoundly affects the final stages of the pathway, causing an increase in lysosomal content accompanied by a significant reduction in the activity of different cathepsins and in the degradation of lysosomal substrates. The evidence that another alpha-herpesvirus with neurotropic properties, HSV-2, induces the same neurodegeneration markers as HSV 1, supports the possible involvement of various infectious agents like as herpesviruses in AD-associated neurodegeneration.<\/p>\n<p style=\"text-align: justify;\">The results of the functional and genetic\/biomarker association studies developed so far support the hypothesis that lysosomal function failure could constitute a relevant mechanism in HSV-1-induced neurodegeneration and, in general, in AD type neurodegeneration, so our group is focused on the study of this functional pathway. Currently, we are developing more complex cell models, based on human NPCs, to validate our previous findings in a more physiological environment and delve deeper into the mechanisms involved.<\/p>\n<p style=\"text-align: justify;\">In addition, we participate in several collaborative projects. The most numerous are those aimed to study the genetic architecture of AD, within the framework of the Spanish Consortium for Dementia Genetics (DEGESCO) and the international consortia EADB and IGAP, which continue to reveal new factors and relevant functions in the pathogenesis of this disease.<\/p>\n<p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=&#8221;1&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; background_color=&#8221;rgba(0,0,0,0.04)&#8221; da_disable_devices=&#8221;off|off|off&#8221; global_colors_info=&#8221;{}&#8221; da_is_popup=&#8221;off&#8221; da_exit_intent=&#8221;off&#8221; da_has_close=&#8221;on&#8221; da_alt_close=&#8221;off&#8221; da_dark_close=&#8221;off&#8221; da_not_modal=&#8221;on&#8221; da_is_singular=&#8221;off&#8221; da_with_loader=&#8221;off&#8221; da_has_shadow=&#8221;on&#8221;][et_pb_row _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; 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