{"id":279829,"date":"2024-07-31T09:00:19","date_gmt":"2024-07-31T07:00:19","guid":{"rendered":"https:\/\/dhcp205002.cbm.uam.es\/?page_id=279829"},"modified":"2025-07-07T10:34:27","modified_gmt":"2025-07-07T08:34:27","slug":"molecular-basis-of-huntingtons-disease-and-other-central-nervous-system-disorders","status":"publish","type":"page","link":"https:\/\/www.cbm.uam.es\/index.php\/scientific-programs\/physiological-and-pathological-processes\/molecular-neuropathology\/molecular-basis-of-huntingtons-disease-and-other-central-nervous-system-disorders\/","title":{"rendered":"Molecular basis of Huntington’s disease and other central nervous system disorders"},"content":{"rendered":"

[et_pb_section fb_built=”1″ _builder_version=”4.27.0″ _module_preset=”default” background_color=”#34609B” background_image=”https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/07\/iStock-1356994685small-scaled.jpg” background_position=”bottom_center” background_vertical_offset=”32%” min_height=”352px” height=”294px” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row column_structure=”2_5,3_5″ use_custom_gutter=”on” gutter_width=”4″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”RGBA(255,255,255,0)” custom_margin=”61px||||false|false” custom_padding=”||0px|||” global_colors_info=”{}”][et_pb_column type=”2_5″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”rgba(52,96,155,0.83)” custom_padding=”50px||50px|50px|false|false” border_radii=”on|15px|15px|15px|15px” global_colors_info=”{}”][et_pb_text _builder_version=”4.25.0″ _module_preset=”default” text_text_color=”#FFFFFF” custom_margin=”0px||10px||false|false” custom_padding=”0px||0px||false|false” global_colors_info=”{}”]<\/p>\n

Scientific Program<\/p>\n

[\/et_pb_text][et_pb_heading title=”Physiological and pathological processes” _builder_version=”4.25.0″ _module_preset=”default” title_font=”Montserrat||||||||” title_text_color=”#FFFFFF” title_font_size=”43px” global_colors_info=”{}”][\/et_pb_heading][\/et_pb_column][et_pb_column type=”3_5″ _builder_version=”4.23.4″ _module_preset=”default” custom_padding=”157px||||false|false” global_colors_info=”{}”][et_pb_text _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n

UNITS IN THIS PROGRAM
\n<\/span><\/h4>\n
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\nMolecular neuropathology<\/a><\/span>\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0Metabolic and signaling networks in disease<\/a><\/span><\/h6>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_enable_image=”off” background_size=”custom” background_image_height=”84%” background_position=”bottom_right” custom_margin=”||0px||false|false” custom_padding=”||0px||false|false” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row _builder_version=”4.23.4″ _module_preset=”default” custom_margin=”||0px||false|false” custom_padding=”||0px||false|false” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_heading title=”RESEARCH GROUP” _builder_version=”4.25.0″ _module_preset=”default” title_level=”h5″ title_text_color=”#13B5BD” custom_margin=”50px||0px||false|false” global_colors_info=”{}”][\/et_pb_heading][et_pb_blurb title=”Molecular basis of Huntington’s disease and other central nervous system disorders” use_icon=”on” font_icon=”||divi||400″ icon_color=”#13B5BD” icon_placement=”left” image_icon_width=”26px” content_max_width=”1100px” content_max_width_tablet=”1100px” content_max_width_last_edited=”off|desktop” _builder_version=”4.25.0″ header_level=”h1″ header_font=”Montserrat||||||||” header_text_color=”#000000″ header_font_size=”29px” header_line_height=”1.4em” body_font=”||||||||” body_font_size=”15px” body_line_height=”1.8em” image_icon_custom_margin=”6px||||false|false” background_layout=”dark” custom_margin=”|||” custom_padding=”||14px||false|false” animation_style=”slide” animation_direction=”right” animation_intensity_slide=”10%” animation=”off” image_max_width=”64px” global_colors_info=”{}”][\/et_pb_blurb][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”rgba(175,218,249,0.18)” custom_padding=”0px||0px||false|false” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row column_structure=”1_4,3_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”1_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”\/imgs\/202.jpg” title_text=”202″ align=”right” module_class=”roundedImg” _builder_version=”4.27.4″ _module_preset=”default” hover_enabled=”0″ global_colors_info=”{}” sticky_enabled=”0″][\/et_pb_image][\/et_pb_column][et_pb_column type=”3_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_heading title=”Jose J. Lucas” _builder_version=”4.25.0″ _module_preset=”default” title_level=”h3″ title_text_align=”left” title_text_color=”#008C93″ global_colors_info=”{}”][\/et_pb_heading][et_pb_text _builder_version=”4.25.0″ _module_preset=”default” custom_margin=”-27px||||false|false” link_option_url_new_window=”on” global_colors_info=”{}”]<\/p>\n

\"\"<\/a>
ORCID<\/a><\/p>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”#13B5BD” custom_margin=”0px||0px||false|false” custom_padding=”0px||0px||false|false” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row column_structure=”1_3,1_3,1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_button button_url=”#investiga” button_text=”Research” button_alignment=”center” _builder_version=”4.25.0″ _module_preset=”default” custom_button=”on” button_bg_color=”#34609B” animation_style=”zoom” global_colors_info=”{}”][\/et_pb_button][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_button button_url=”#personal” button_text=”Group members” button_alignment=”center” _builder_version=”4.25.0″ _module_preset=”default” custom_button=”on” button_bg_color=”#34609B” custom_padding=”|44px||44px|false|true” animation_style=”zoom” global_colors_info=”{}”][\/et_pb_button][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_button button_url=”#publica” button_text=”Publications” button_alignment=”center” _builder_version=”4.25.0″ _module_preset=”default” custom_button=”on” button_bg_color=”#34609B” animation_style=”zoom” global_colors_info=”{}”][\/et_pb_button][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_enable_image=”off” background_size=”custom” background_image_height=”84%” background_position=”bottom_right” custom_margin=”0px||0px||false|false” custom_padding=”0px||15px||false|false” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row column_structure=”1_2,1_2″ use_custom_gutter=”on” gutter_width=”2″ _builder_version=”4.23.4″ _module_preset=”default” custom_margin=”20px||||false|false” custom_padding=”||||false|false” global_colors_info=”{}”][et_pb_column type=”1_2″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_text admin_label=”resumen” module_id=”resumen” module_class=”resumen” _builder_version=”4.27.4″ _module_preset=”default” text_font_size=”15px” text_line_height=”1.8em” background_color=”#f1f8fe” custom_padding=”20px|20px|20px|20px|true|false” border_width_top=”1px” border_color_top=”#008C93″ border_width_bottom=”1px” border_color_bottom=”#008C93″ global_colors_info=”{}”]<\/p>\n

We study the molecular basis of brain diseases in order to develop cures. Much of our work studies Huntington’s disease as a paradigmatic disease with a known cause (a mutation), which allows us to generate transgenic mice in which to study the course of the disease. This has revealed molecular processes also altered in many other brain diseases, such as errors in RNA processing (splicing and polyadenylation).<\/p>\n

[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_2″ _builder_version=”4.23.4″ _module_preset=”default” custom_padding=”||||false|false” global_colors_info=”{}”][et_pb_image src=”data:image\/svg+xml;base64,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” title_text=” ” _builder_version=”4.25.0″ _module_preset=”default” animation_style=”zoom” global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_5,2_5″ _builder_version=”4.23.4″ _module_preset=”default” custom_margin=”||||false|false” custom_padding=”0px||||false|false” global_colors_info=”{}”][et_pb_column type=”3_5″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_heading title=”Research” module_id=”investiga” _builder_version=”4.25.0″ _module_preset=”default” custom_margin=”0px|||0px|false|false” custom_padding=”3px|||8px|false|false” border_width_left=”6px” border_color_left=”#34609B” global_colors_info=”{}”][\/et_pb_heading][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n

We study the molecular mechanisms underlying brain diseases by generating genetic mouse models, like the HD94 and Tet\/GSK3 models of Huntington\u2019s and Alzheimer\u2019s, or the TgCPEB4\u03944 model (Nature 560:441-446, 2018; Nature 637:496-503, 2025) of idiopathic autism, to validate pathogenic pathways and to test new therapeutic strategies.<\/p>\n

Huntington\u2019s disease (HD) is an autosomal dominant neurodegenerative disease characterized by involuntary movements, psychiatric symptoms and dementia. It is caused by an expansion of the trinucleotide CAG located in the huntingtin gene. By characterizing the molecular interactions of the mutated RNA and protein, and in particular their impact on RNA binding proteins and RNA processing, we found new clues about HD and other neural disorders like X-linked dystonia parkinsonism (XDP), epilepsy, autism, schizophrenia and multiple sclerosis.<\/p>\n

[\/et_pb_text][\/et_pb_column][et_pb_column type=”2_5″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2025\/07\/2025-07-04-Grupo-JJLucas-05S-1200px.jpg” title_text=”2025-07-04 Grupo JJLucas 05S-1200px” _builder_version=”4.27.4″ _module_preset=”default” custom_margin=”60px||||false|false” custom_padding=”|||27px||” animation_style=”zoom” border_width_all=”3px” border_color_all=”#13B5BD” box_shadow_style=”preset3″ global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.23.4″ _module_preset=”default” custom_padding=”0px||||false|false” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n

For instance, by characterizing the global mis-splicing signature in HD striatum (Brain 143: 2207-19, 2020 & Brain 144:2009-23, 2021) we found an alteration of tau (the protein that accumulate inside neurons in Alzheimer\u2019s disease). By analyzing transgenic HD mouse models with varying levels of tau we demonstrated that tau contributes to HD pathogenesis and we discovered a new histopathological hallmark, the Tau Nuclear Rods or Tau Nuclear Indentations (Nat Med 20:881-5, 2014).<\/p>\n

Characterizing the role of cytoplasmic polyadenylation of mRNAs by CPEBs in HD, we discovered a treatable thiamine deficiency in HD brains (Sci Transl Med 2021 13:eabe7104) which has originated a clinical trial (https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04478734<\/a>).<\/p>\n

We also found that the majority of autism spectrum disorder (ASD) risk genes are targets of CPEB4. In fact, CPEB4 shows an isoform imbalance in individuals with autism due to mis-splicing of a neuronal specific microexon. Accordingly, mice with equivalent CPEB4 imbalance show autism-like phenotype (Nature 560:441-446, 2018; Nature 637:496-503, 2025) and have become a useful model of idiopathic autism.<\/p>\n

We have also described alterations of cytoplasmic polyadenylation system in epilepsy (Brain 143: 2139-53 2020) and schizophrenia (Biol Psychiatry 94:341-351, 2023).<\/p>\n

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fabio.desideri(at)cbm.csic.es<\/p>[\/et_pb_blurb][\/et_pb_column][\/et_pb_row][\/et_pb_code][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”RGBA(255,255,255,0)” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_heading title=”Selected publications” module_id=”personal” _builder_version=”4.25.0″ _module_preset=”default” custom_margin=”0px|||0px|false|false” custom_padding=”3px|||8px|false|false” border_width_left=”6px” border_color_left=”#34609B” global_colors_info=”{}”][\/et_pb_heading][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_4,1_4,1_4,1_4″ _builder_version=”4.23.4″ _module_preset=”default” animation_style=”zoom” global_colors_info=”{}”][et_pb_column type=”1_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/06\/1-Imagen-Jose-Lucas-Lab-209.png” title_text=” ” url_new_window=”on” _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.25.0″ _module_preset=”default” link_option_url=”https:\/\/pubmed.ncbi.nlm.nih.gov\/34586830\/” link_option_url_new_window=”on” global_colors_info=”{}”]<\/p>\n

CPEB alteration and aberrant transcriptome-polyadenylation lead to a treatable SLC19A3 deficiency in Huntington’s disease<\/h3>\n

Sara Pic\u00f3 et al.<\/p>\n

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Huntington’s disease-specific mis-splicing unveils key effector genes and altered splicing factors<\/h3>\n

Ainara Elorza et al.<\/p>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_4,1_4,1_4,1_4″ _builder_version=”4.23.4″ _module_preset=”default” animation_style=”zoom” global_colors_info=”{}”][et_pb_column type=”1_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/06\/3-Imagen-Jose-Lucas-Lab-209.png” title_text=” ” url_new_window=”on” _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.25.0″ _module_preset=”default” link_option_url=”https:\/\/pubmed.ncbi.nlm.nih.gov\/30111840\/” link_option_url_new_window=”on” global_colors_info=”{}”]<\/p>\n

Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing<\/h3>\n

Alberto Parras et al.<\/p>\n

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Title<\/h3>\n

Authors<\/p>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”rgba(0,0,0,0.04)” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_heading title=”Latest publications” module_id=”publica” _builder_version=”4.25.0″ _module_preset=”default” custom_margin=”0px|||0px|false|false” custom_padding=”3px|||8px|false|false” border_width_left=”6px” border_color_left=”#34609B” global_colors_info=”{}”][\/et_pb_heading][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”][et_pb_code _builder_version=”4.25.2″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n

Cargando publicaciones…<\/div>\n